University of Southern California Dissertations and Theses

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

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Content THE EFFECT OF THE pH OF PERFUSATES OH THE ACTIVITY OF THE INTACT URINARY BLADDER IN THE RAT A T h e sis P re s e n te d to th e F a c u lty o f th e D epartm ent o f Zoology U n i v e r s i t y o f S o u th e rn C a l i f o r n i a I n P a r t i a l F u l f i l l m e n t o f th e R equirem ents f o r th e D egree M a ste r of S c ie n c e by G lo r ia G allo A ugust 1950 UMl 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 issoftation Publishing UMl EP67180 Published by ProQuest LLC (2014). Copyright in the Dissertation held by the Author. Microform Edition © ProQuest LLC. All rights reserved. This work is protected against unauthorized copying under Title 17, United States Code ProQuest LLC. 789 East Eisenhowei Parkway P.O. Box 1346 Ann Arbor, Ml 48106- 1346 TAij thesis, nvritten by P.lar.la.V.alLo.................................................... under the guidance of h..?X... Faculty Committee, and approved by all its members, has been presented to and accepted by the Council on Graduate Study and Research in partial fulfill ment of the requirements for the degree of Master o f Science Department o f 7oolopy Faculty Committee 'f - f : ...................... Chairman .... TABLE OP CONTENTS CHAPTER PAGE I . INTRODUCTION S ta te m e n t o f th e problem .................................................... 1 Im p o rtan ce o f th e problem .................................................... 1 I I . REVIEW OP THE LITERATURE The p h y s io lo g y of smooth m uscle .................................... 3 The p h y s io lo g y of m i c t u r i t i o n .............................. 12 I n n e r v a t i o n o f th e u r i n a r y b la d d e r . . . . . . 13 Component r e f l e x e s o f m i c t u r i t i o n .......................... . 1 6 I I I . EXPERIMENTAL DATA Methods and m a t e r i a l s ........................................ 25 Methods o f d e c e r e b r a t i o n and r e s u l t s o b ta in e d . 26 R ec o rd in g a p p a r a tu s . . . . . ......................................... 33 R ec o rd in g p ro c e d u re ......................................................... . 40 P e r f u s a t e s u s e d , th e c o m p o sitio n of b u f f e r s o l u t i o n s ....................................................................... 43 P r e s e n t a t i o n of e x p e r im e n ta l d a t a ......................... 47 R e s u l t s .................................................................................................. 50 IV. DISCUSSION OF EXPERIMENTAL RESULTS M i c t u r i t i o n i n th e d e c e r e b r a t e r a t ...............................94 The e f f e c t of n em butal a n e s t h e s i a ............................... 94 The e f f e c t of a c i d and a l k a l i n e p e r f u s a t e s on th e tone of th e d e t r u s o r m uscle and th e b la d d e r s p h i n c t e r ........................................ 96 i l l CHAPTER PAGE V. SUMMARY AND CONCLUSIONS Summary ............................... 101 C o n c l u s i o n s ............................................................. 102 VI. DIDLIOGRAPIIY......................................................................................... 104 LIST OF TABLES TABLE PAGE I . The Component R e fle x e s o f M i c t u r i t i o n - - B a r r i n g t o n 24 tt I I . S o r e n s e n ’ s B u ffe r M ix tu res ..................................... . . . 44 I I I . Rat # 1 — D e c e r e b r a te . A n a ly s is o f Kymogram Showing R e s u l t a n t V e s ic a l P r e s s u r e s U sing S a l i n e P e r f u s a t e ........................................................................ 50 IV. Rat # 2 —D e c e r e b r a te . A n a ly s is of Kymogram Showing R e s u l t a n t V e s ic a l P r e s s u r e s U sing S a lin e P e r f u s a t e ........................................................................ 5 V. R at # 2 —D e c e r e b r a te . A n a ly s is of Kymogram Showing R e s u l t a n t V e s ic a l P r e s s u r e s U sing S a l i n e P e r f u s a t e ........................................................................ 53 VI. Rat # 2 —D e c e r e b r a te . A n a ly s is of Kymogram Showing R e s u l t a n t V e s ic a l P r e s s u r e s U sing P e r f u s a t e , pH 1 . 0 5 ................................................................... 55 V II. R at # 2 —D e c e r e b r a te . A n a ly s is of Kymogram Showing R e s u l t a n t V e s ic a l P r e s s u r e s U sing S a l i n e P e r f u s a t e ........................................................................ 56 V I I I . R at # 3 --H em b u tal A n e s th e s ia . A n a ly s is of Kymogram Showing R e s u l t a n t V e s ic a l P r e s s u r e s U sin g S a lin e P e r f u s a t e ......................................................... 58 IX. R at # 3 --N em butal A n e s th e s ia . A n a ly s is of Kymogram Showing R e s u l t a n t V e s ic a l P r e s s u r e s U sin g P e r f u s a t e , pH 3 . 3 .................................................... 59 X. Rat #3--Decerebrate. Analysis of Kymogram Showing R e s u l t a n t V e s ic a l P r e s s u r e s U sin g S a lin e P o rfu o a to ................................................................... G1 XI. Rat # 3 — D e c e r e b r a te . A n a ly s is of Kymogram Showing R e s u l t a n t V e s ic a l P r e s s u r e s U sing P e r f u s a t e , pH 3 . 3 ................................................................... 62 X II. Rat # 4 --H em butal A n e s th e s ia . A n a ly s is of Kymogram Showing R e s u l t a n t V e s ic a l P r e s s u r e s U sing S a lin e P e r f u s a t e ......................................................... 64 X I I I . Rat #4--N em b u tal A n e s th e s ia . A n a ly s is of Kymogram Showing R e s u l t a n t V e s ic a l P r e s s u r e s U sing S a lin e P e r f u s a t e ................................................65 XIV. R at # 4 —D e c e r e b r a te . A n a ly s is of Kymogram Showing R e s u l t a n t V e s ic a l P r e s s u r e s U sin g S a lin e P e r f u s a t e ......................................................... 67 XV. Rat # 4 - - D e c e r e b r a t e . A n a ly s is of Kymogram Showing R e s u l t a n t V e s ic a l P r e s s u re s U sing P e r f u s a t e , pH 3 . 3 ............................................................................68 XVI. R at # 4 - - D e c e r e b r a t e . A n a ly s is o f Kymogram Showing R e s u l t a n t V e s ic a l P r e s s u r e s U sing P e r f u s a t e , pH 3 . 3 ................................................... 69 XVII. Rat # 5 --D 0 c e r e b r a t e . A n a ly s is of 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 sing S a lin e P e r f u s a t e ........................................................................ 71 XVIII. Rat #5--D0oere'brat0. Analysis of Kymogram Showing R e s u l t a n t V e s ic a l P r e s s u r e s U sing P e rfu s a L e , pH 4 . 5 2 ............................................................... 72 XIX. Rat # 5 - - D e c e r e b r a te . A n a ly s is o f Kymogram Showing R e s u l t a n t V e s ic a l P r e s s u re s U sing P e r f u s a t e , pH 8 . 4 .................................................................... 73 XX. R at # 6 - - D s c e r e b r a t e . A n a ly s is o f Kymogram Showing R e s u l t a n t V e s ic a l P r e s s u r e s U sing S a l i n e P e r f u s a t e ........................................................................ 75 XXI. R at # 6 — D e c e r e b r a te . A n a ly s is of Kymogram Showing R e s u l t a n t V e s ic a l P r e s s u r e s U sing P e r f u s a t e , pH 4 . 5 2 .......................................................................... 76 XXII. R at # 6 —D e c e r e b r a te . A n a ly s is of Kymogram Showing R e s u l t a n t V e s ic a l P r e s s u r e s U sing P e r f u s a t e , pH 8 . 4 ................................................................. 78 X X III. Rat # 6 —D e c e r e b r a te . A n a ly s is o f Kymogram Showing R e s u l t a n t V e s ic a l P r e s s u r e s U sing P e r f u s a t e , pH 4 . 5 2 .......................................................................79 XXIV. R at # 7 —D e c e r e b r a te . A n a ly s is o f Kymogram Showing R e s u l t a n t V e s ic a l P r e s s u r e s U sing S a l i n e P e r f u s a t e ........................................................................ 81 XXV. R at # 7 - - D e c e r e b r a t e . A n a ly s is o f Kymogram Showing R e s u l t a n t V e s ic a l P r e s s u r e s U sing P e r f u s a t e , pH 4 . 5 2 .......................................................................82 84 XXVI. Rat -#7--Decerebrate. Analysis of Kymogram Showing R e s u l t a n t V e s ic a l P r e s s u r e s U sing P e r f u s a t e , pH 9 .1 . . . . .................................... XXVII. Rat # 7 - - D e c e r e b r a t e . A n a ly s is o f Kymogram Showing R e s u l t a n t V e s ic a l P r e s s u r e s U sing P e r f u s a t e , pH 4 . 5 2 .........................................................................85 XXVIII. Rat # 8 —D e c e r e b r a te . A n a ly s is o f Kymogram Comparing V e s ic a l P r e s s u r e s U sing P e r f u s a t e , pH 5 .8 8 and I s o s m o la r S a lin e P e r f u s a t e . XXIX. R at # 8 - - D e c e r e b r a t e . A n a ly s is o f Kymogram Comparing V e s ic a l P r e s s u r e s U sin g P e r f u s a t e , pH 9 .1 and I s o s m o la r S a lin 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 a ly s is of Kymogram Comparing V e s ic a l P r e s s u r e s U sing P e r f u s a t e , pH 2 .1 8 and I s o s m o la r S a lin e P e r f u s a t e . 87 89 91 XXXI. Summary of E x p e rim e n ta l R e s u l t s .............................................93 LIST OP FIGURES FIGURE PAGE 1. Diagram of th e R ec o rd in g A p p a ra tu s Showing th e S e t Up f o r C a l i b r a t i n g th e S y s t e m ............................... 36 2. The A p p a ra tu s As S e t Up F or R ec o rd in g I n t r a v e s i c a l P r e s s u r e s i n th e R at . . . . . . . . . . . 37 3. P hoto g rap h Showing th e C o n c e n tric Cannulae I n s e r t e d I n t o th e U r in a ry B la d d e r . . . . . . ..................... 38 4. T y p ic a l C a l i b r a t i o n Curve . . . . . . . . . . . . 41 5. P hoto g rap h of An O r ig in a l Kymogram Showing 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 ario u s P e r f u s a t e s i n D e c e r e b r a te Rat #8 . . . 49 6. R at # l - “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 and V e s ic a l P r e s s u re U sing S a l i n e P e r f u s a t e ........................................................................ 51 7. Rat # 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 and V e s ic a l P r e s s u r e U sing S a l i n e P e r f u s a t e s ........................................................................ 54 8 . 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 and V e s ic a l P r e s s u re U sing A cid and S a l i n e P e r f u s a t e s ...................................... . . . . . . 57 9. R at # 3 —Nembutal A n e s th e s ia . G ra p h ic a l R e l a t i o n s h i p o f Volume I n j e c t e d and V e s ic a l P r e s s u re U sing Acid and S a lin e P e r f u s a t e s ..........................................................60 10. Rat # 3 - - D e c e r e b r a t8 . G ra p h ic a l R e l a t i o n s h i p o f Volume I n j e c t e d and V e s ic a l P r e s s u r e U sing A cid and S a l i n e P e r f u s a t e s ............................................... 63 11. R at # 4 —Nem butal A n e s th e s ia . G ra p h ic a l R e l a t i o n s h i p o f Volume I n j e c t e d and V e s ic a l P r e s s u r e U sing S a lin e P e r f u s a t e s ........................................................................ 66 12. R at # 4 - “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 o f Volume I n j e c t e d and V e s ic a l P r e s s u r e U sing S a lin e and A cid P e r f u s a t e s ..........................................................70 13. R at # 5 - - 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 o f Volume I n j e c t e d and V e s ic a l P r e s s u re U sing S a l i n e , A cid and B asic P e r f u s a t e s ............................... 74 14. R at # 6 — D e c e r e b r a te . G ra p h ic a l R e l a t i o n s h i p o f Volume I n j e c t e d and V e s ic a l P r e s s u r e U sing S a lin e and A cid P e r f u s a t e s ............................................... 77 15. Rat # 6 — D e c e r e b r a te . G ra p h ic a l R e l a t i o n s h i p o f Volume I n j e c t e d and V e s ic a l P r e s s u r e U sing B asic and A cid P e r f u s a t e s .................................................... 80 16. R at # 7 — D e c e r e b r a te . G ra p h ic a l R e l a t i o n s h i p o f Volume I n j e c t e d and V e s ic a l P r e s s u r e U sing S a lin e and Acid P e r f u s a t e s ..........................................................83 17. R at # 7 - - 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 o f Volume I n j e c t e d and V e s ic a l P r e s s u re Using B asic and A cid P e r f u s a t e s ................................................... 86 18. R at # 8 --D ec e r e b r a t e . G r a p h ic a l R e l a t i o n s h i p o f Volume I n j e c t e d and V e s ic a l P r e s s u r e Using I s o s m o la r S a lin e and Acid P e r f u s a t e s . . . . . 88 19. R at # 8 - - 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 o f Volume I n j e c t e d and V e s ic a l P r e s s u r e U sing Is o s m o la r S a lin e and B asic P e r f u s a t e s ..................... 90 20. R at # 8 —D e c e r e b r a te . G ra p h ic a l R e l a t i o n s h i p o f Volume I n j e c t e d and V e s ic a l P r e s s u r e U sing I s o s m o la r S a lin e and A cid P e r f u s a t e s . . . . . . 92 CHAPTER I INTRODUCTION As e a r l y as 1902, Dixon s t u d i e d the e f f e c t s of a c id s and b a se s on smooth m u sc le ; Evans and U n d e r h i l l , i n 1923, a l s o ob serv ed th e e f f e c t s of a l t e r a t i o n of h y d ro g e n -io n c o n c e n t r a t i o n on tone and c o n t r a c t i o n s o f smooth m u sc le . I n th e s e i n v e s t i g a t i o n s , e x p e rim e n ts were c a r r i e d o u t on e x c is e d smooth m uscle s t r i p s ; b a t h i n g i n a s o l u t i o n of a c id pH was found to cau se d e c r e a s e d to n e and d e c r e a s e d c o n t r a c t i o n s w h ile a l k a l i n e pH was found to cau se 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 th e e f f e c t of th e pH of p e r f u s a t e s on th e i n t a c t u r i n a r y b l a d d e r i n th e r a t i s an a tte m p t to s tu d y n o t o n ly th e r e a c t i o n o f th e i n t a c t v e s i c a l m u s c u la tu re i n s i t u to a c id and b a s ic s o l u t i o n s , b u t a l s o to o b serv e th e o v e r a l l e f f e c t of t h i s r e a c t i o n w ith r e l a t i o n to th e re sp o n se o f th e b la d d e r s p h i n c t e r and th e m i c t u r i t i o n r e f l e x . I f th e e f f e c t of a l k a l i n e p e r f u s a t e s on th e smooth m u sc u la tu re of th e i n t a c t u r i n a r y b la d d e r i s th e same as th e e f f e c t on e x c is e d s t r i p s of smooth m u scle, t h a t i s i n c r e a s e d to n e , such an e f f e c t m ight be of v a lu e c l i n i c a l l y as the p o s s i b l e 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 i n some i n d i v i d u a l s s in c e i t i s p o s s i b l e t h a t e x c e s s i v e l y a l k a l i n e u r i n e m ight a c t i n th e same manner as th e a l k a l i n e p e r f u s a t e . And lik e w i s e i f th e e f f e c t of h ig h h y d ro g e n -io n c o n c e n t r a t i o 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 llo w in g l a r g e b la d d e r volumes 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 , i t seems l i k e l y t h a t i t m ig h t be a p p l i e d as th e r a p y f o r e l i m i n a t i n g b la d d e r c a l c u l i . A s i m i l a r p r i n c i p a l , t h a t of a llo w in g the b l a d d e r to become g r e a t l y d i s te n d e d , h as been e f f e c t i v e l y a p p l i e d i n e x p e l l i n g g a l l s to n e s from the g a l l b l a d d e r . C e r t a i n l y , th e pH o f u r i n e can be c o n t r o l l e d by d i e t a r y m eans, s in c e c e r t a i n foods a r e a c id - f o r m in g w h ile o t h e r s a r e b a s e -f o rm in g . V e g e ta b le s and f r u i t s on b e in g m e ta b o liz e d , le a v e an a sh i n which th e b a s ic e lem en ts sodium, p o ta ssiu m and ca lc iu m p r e d o m in a te . M eats, f i s h f o o d s , eggs and o th e r h ig h p r o t e i n fo o d s le a v e an ash i n which p re d o m in a n tly a c id o r fo rm in g e le m e n ts , c h l o r i n e , p h o sphorus and s u l f u r p re d o m in a te . Thus th ro u g h consum ption of e i t h e r a c id - fo r m in g or b a s e -fo rm in g f o o d s , th e pH of th e u r i n e c o u ld be c o n t r o l l e d . U r in a ry pH m ig h t a l s o be a l t e r e d by 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 which a c i d i f i e s , or sodium b i c a r b o n a t e which a l k a l i z e s . VJhile c o n t r o l l e d pH i s u sed to p r e v e n t fo rm a tio n of u r i n a r y c a l c u l i by e l i m i n a t i n g th e optimum 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 u sed as t h e r a p e u t i c m easure f o r e x p e l l i n g a l r e a d y formed c a l c u l i . CHAPTER I I REVIEW OP THE LITERATURE S in ce 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 v/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 th e a c t i v i t y of th e smooth m uscle o f th e u r i n a r y "bladder 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 , an e f f e c t i v e p r e s e n t a t i o n and e v a l u a t i o n o f th e r e s u l t s r e q u i r e s an u n d e r s ta n d i n g o f th e g e n e r a l p r o p e r t i e s o f smooth m uscle and th e c h a r a c t e r i s t i c s o f th e m i c t u r i t i o n r e f l e x . T h e re f o re , a re v ie w o f some o f th e l i t e r a t u r e i n th e f i e l d o f smooth m uscle p h y s io lo g y and th e m i c t u r i t i o n r e f l e x i s p r e s e n te d h e r e w i t h . Li t e r a t u r e on th e p h y s io lo g y o f smooth m u s c le . The p h y s io lo g y o f smooth m uscle h as b een a s u b j e c t o f q u i t e e x t e n s i v e i n v e s t i g a t i o n b u t as p o in te d o u t by F i s c h e r (1 9 4 4 ), i n h i s re v ie w o f v e r t e b r a t e smooth m u s c le ,a g r e a t d e a l of d is a g re e m e n t and la c k o f p r e c i s e knowledge e x i s t s to d a y . C.L. Evans (1 9 2 6 ), i n a re v ie w o f th e p h y s io lo g y o f smooth m uscle em phasized two re a s o n s f o r th e i n d e f i n i t e s t a t e o f know ledge: 1 ) . g e n e r a l i z a t i o n c o n c e rn in g p r o p e r t i e s of p l a i n m uscle from e x p e rim e n ts on one type o f a n im a l have been made; 2 ) . p l a i n m uscle h as a c o m p lic a te d r e l a L l o n s h lp of th e t i s s u e to i t s 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 o n ly 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 s i o l o g i c a l l y , and 4 p h a r m a c o lo g ic a lly n o t o n ly i n v a r io u s s tr i a t e d , m u scles i n one an im a l b u t a l s o i n o t h e r c l a s s e s o f v e r t e b r a t e s . Smooth m u scles 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 i n d i f f e r e n t organs i n th e same a n im 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 o rg an s o f r e l a t e d s p e c i e s . I n v e r t e b r a t e s , smooth m uscle may be a rra n g e d i n two o r more l a y e r s , each c a p a b le o r c o n t r a c t i n g in d e p e n d e n tly and w ith f i b e r s ru n n in g i n d i f f e r e n t d i r e c t i o n s . Thus i t can r e a d i l y be seen t h a t smooth m uscle 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 g e n e r a l i z a t i o n s m ig h t le a d to c o n f u s io n . As m en tio n ed ab o v e, th e c o m p lic a tin g f a c t o r of n e rv e s u p p ly a l s o le a d s to c o n f u s io n i n i n t e r p r e t a t i o n o f r e s u l t s . N e a rly a l l smooth m uscle 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 rv e su p p ly th e components o f which have o p p o s ite f u n c t i o n s , and t h i s s u p p ly may e x i s t as g a n g lio n ic c e l l s and p le x u s e s o f n e rv e f i b e r s w i t h i n th e t i s s u e so t h a t i t i s d i f f i c u l t to d e te rm in e w h e th e r th e o b serv ed e f f e c t s a r e a t t r i b u t a b l e t o th e m uscle i t s e l f , th e a n t a g o n i s t i c n e r v e s , th e i n t r i n s i c n e r v e s , o r c o m b in a tio n of th e s e f a c t o r s . C om plexity o f th e v e r t e b r a t e smooth m uscle h a s le d to th e u se of c e r t a i n i n v e r t e b r a t e smooth m uscles which a r e f r e e from an i n t r i n s i c su p p ly o f n e r v e s . Smooth m uscle 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 ab sen ce of o r o s s - s t r i a t i o n s and p h y s i o l o g i c a l l y by slow ness o f movement. B o z le r, (1941) c l a s s i f i e d v e r t e b r a t e m uscles as fo llo w s : Smooth mus c l e s ; 1« Those a c t i v a t e d by tr u e m otor n e r v e s 2, Those r h y th m i c a l l y a c t i v e by v i r t u e of 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 sc le s: ^many u n i t s ) m u l t i - u n i t ^ ^ s k e l e t a l imotor nerves^ smooth S t r i a t e d m uscle m uscle ^ c a r d ia c r s y n c y t i a l / (a u to m a tic j v i s c e r a l Smooth m u scles i n th e f i r s t group c o n s i s t o f many s m a ll u n i t s s i m i l a r to s k e l e t a l m uscle i n a rra n g e m e n t. These a r e u n d e r more 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 of the n e r v e s , and e x h i b i t l e s s sp o n tan e o u s r h y t h m i c i t y . R e p r e s e n t a t i v e s of th e group a r e b lo o d v e s s e l s , and n i c t a t i n g membranes. I n th e second group, n e rv e s may be p r e s e n t , b u t a r e n o t i n d i s p e n s a b l e f o r c o n t r a c t i o n , s in c e th e m u scles th em se lv 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 th m ic a l movement. P l a i n m u scles o f th e h o llo w v i s c e r a a r e of t h i s type such as th e i n t e s t i n e and u r i n a r y b l a d d e r . I t i s g e n e r a l l y a g re e d t h a t th e m a j o r i t y of organs c o n s i s t i n g of smooth m uscle ele m e n ts r e c e i v e e f f e r e n t n e rv e f i b e r s from sy m p a th e tic and p a ra s y m p a th e tic d i v i s i o n s o f th e autonom ic n erv o u s sy stem . The h i s t o l o g i c a l d e t a i l o f th e r e l a t i o n s h i p betw een n e rv e s and m uscle c e l l s i s s t i l l a m a t t e r o f u n c e r t a i n t y . 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 as a r u l e , n e rv e en d in g s s u p p ly a m a j o r i t y of m uscle c e l l s . However, t h e r e i s a wide d i f f e r e n c e i n th e d e g re e of dependence o f th e smooth m uscle on i t s i n n e r v a t i o n . V h eth er or n o t a l l th e myons 6 a r e u n d e r d i r e c t i n f l u e n c e of b o th system s i s a m a t t e r of q u e s ti o n . Gannon and R o se n b lu e th (1937), p r e s e n te d ev id e n c e t h a t only a f r a c t i o n o f th e c e l l s r e c e i v e n e rv e e n d in g s . Because of th e ev id en ce t h a t o n ly a f r a c t i o n of th e smooth m uscle c e l l s r e c e i v e n e r v e e n d in g s, some have i n t e r p r e t e d t h i s to mean t h a t r e s p o n s e s of smooth m uscle a re graded and m uscle c e l l s do n o t resp o n d i n th e a l l - o r - n o n e mariner o f s t r i a t e d m uscle b ecau se c o n t r a c t i o n of m uscles i s b ro u g h t a b o u t by l i b e r a t i o n o f ch em ical m e d ia to rs which d i f f u s e and a c t i v a t e o th e r c e l l s p ro d u c in g a grad ed r e s p o n s e . B o z le r, (1 9 3 8 ), d e m o n stra te d p h y s i o l o g i c a l l y t h a t c o n t r a c t i o 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 s p o n ta n e o u s ly . The g r a d in g of s t r e n g t h of c o n t r a c t i o n he e x p la in e d as b e in g due to i n t e n s i t y of d i s c h a r g e of im p u lses co n d u cted w i t h i n the m u scle, and to th e s i z e o f th e p o t e n t i a l which may v a ry w ith th e p h y s i o l o g i c a l c o n d i t i o n of th e t i s s u e . A c t i v i t y o f smooth m u sc le , th e n , he co n clu d ed i s due to d i s c h a rg e s of im p u lses w hich a re 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 s c le s . V a r i a b i l i t y of re sp o n s e o c c u rs , how ever, due to f re q u e n c y , number o f im p u lses d is c h a r g e d , r a t e of con d u c tio n or v a r i a t i o n s in e x c i t a b i l i t y . B o z le r (1 9 4 1 ), demon s t r a t e d t h a t e x c i t a b i l i t y i n s t r i p s of u t e r u s v a r i e s w ith th e p re s e n c e and absence of e s t r o g e n . Thus i n th e s tu d y o f re sp o n s e s of smooth m uscle i t i s im p o rta n t to c o n s id e r n o t o n ly th e p h t s i o l o g i c a l c o n d i t i o n of th e m u sc le , b u t a l s o i t i s im p o rta n t to c o n s id e r th e d i f f e r e n c e s i n o r g a n i z a t i o n of v a r io u s m u scles i n r e g a r d to th e mechanism of c o o r d i n a t i o n o f a c t i v i t y of m uscle f i b e r s s in c e i n some organs c o o r d i n a t i o n m ig h t be e f f e c t e d th ro u g h th e c e n t r a l n ervous system and m otor n e r v e s , w h ile i n o th e r o rg an s c o o r d i n a t i o n m ight be a c c o m p lis h ed by s y n c y t i a l c o n n e c tio n and t r a n s m i s s i o n . B o z le r (1 9 3 6 ), i n v e s t i g a t e d i n v e r t e b r a t e smooth m u sc le , 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 th e a d d u c to r o f P e c te n , and co n clu d ed t h a t th e mechanism o f c o n t r a c t i o n of smooth m uscle and s t r i a t e d m uscle i s fu n d a m e n ta lly th e same. I n h i s s tu d y , th e m uscle was c o n s id e re d u n d e r two d i f f e r e n t c o n d i t i o n s ; 1. R eco rd in g th e changes o f l e n g th u n d e r c o n s ta n t lo a d . 2 . R ecording th e changes o f t e 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 i t i o n , i t was n o te d t h a t a lo a d a p p l i e d to a m u scle cau se d f i r s t a sudden e x t e n s io n o f th e m uscle which th e n c o n tin u e d to le n g th e n v e ry slo w ly . A f t e r u n lo a d in g th e r e was no r e t u r n to th e fo rm er l e n g t h u n l e s s s t i m u l a t e d . The change o f le n g t h was v e ry slow i n d i c a t i n g v is c o u s r e s i s t a n c e . The speed o f r e l a x a t i o n th u s seemed to depend on th e v i s c o s i t y o f th e m u sc le . S in ce i t h as b een shown by G asser and H i l l (1 9 2 4 ), t h a t th e v i s c o s i t y o f s k e l e t a l m uscle i s i n c r e a s e d d u r in g c o n t r a c t i o n , t h e r e i s a p o s s i b i l i t y o f r e l a t i o n s h i p betw een v i s c o s i t y of smooth m uscle and to n u s . Under th e second c o n d i t i o n , th e e l a s t i c t e n s i o n p roduced w h ile th e m uscle was 8 b e in g s t r e t c h e d was n o te d . I t was o b serv ed t h a t as soon as th e l e n g t h was m a in ta in e d c o n s t a n t , te n s i o n dropped o r d i s a p p e a r ed i n a few m in u te s w ith 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 i s i n t e r e s t i n g to n o t e , t h a t i f th e m uscle was f i r s t s t i m u l a t e d , and a t th e end o f r e l a x a t i o n th e m uscle was s t r e t c h e d 10^ o f i t s l e n g t h , i t was found t h a t th e r e l e a s e o f t e n s i o n fo llo w e d th e same tim e c o u rs e as th e r e l a x a t i o n of an i s o m e t r i c c o n t r a c t i o n , and as th e r e l a x a t i o n was made f a s t e r or slo w e r by ch an g in g c o n d i t i o n s , th e tim e r e l a t i o n s o f th e r e l e a s e of t e n s i o n changed c o r r e s p o n d in g ly . I t can be seen t h a t c o n t r a r y to an e l a s t i c body, th e t e n s i o n d is a p p e a re d i f th e le n g t h was m a in ta in 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 uscle and s u g g e s tin g a r e a rra n g e m e n t of e le m e n ta ry p a r t i c l e s w it h i n th e m uscle p ro to p la s m . Smooth m u scle 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 th e c a se o f th e m u s c u la tu r e o f th e u r i n a r y b l a d d e r , t e n s i o n may have a tw o - fo ld e f f e c t . I f th e b la d d e r i s d e n e r v a te d and f l u i d i s i n j e c t e d i n t o i t s lo w ly , th e e f f e c t o f t e n s i o 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 ll so t h a t a c o n s id e r a b l e amount of f l u i d can be t o l e r a t e d w ith o u t any g r e a t r i s e i n p r e s s u r e . 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 r r i n g . With c o n tin u e d I n j e c t i o n , i f th e l e v e l of t o l e r a n c e i s s u r p a s s e d , th e b la d d e r w a ll b e g in s to d i s t e n d p a s s i v e l y and t h i s i n c r e a s e d t e n s i o n s t i m u l a t e s n o t a r e l a x a t i o n , b u t an o c c u rre n c e o f rh y th m ic c o n t r a c t i o n s o f th e whole b l a d d e r which f i n a l l y 9 r e s u l t s i n em ptying o f th e b l a d d e r . C h a r a c t e r i s t i c a l l y , smooth m uscle e x h i b i t s th e p r o p e r t y o f to n u s which i s i n e f f e c t a s t a t e o f c o n tin u e d c o n t r a c t i o n and i s c h a r a c t e r i z e d by a v e ry slow change i n m a g n itu d e . The d e g re e o f tonus has been shown by Winton (1930) to v a ry w ith th e so u rc e o f t i s s u e . C.L. Evans (1923) showed t h a t smooth m uscle i n a s t a t e o f tonus h as no h i g h e r oxygen consum ption th an 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 of oxygen i s e s s e n t i a l f o r th e m a in te n a n c e of to n u s . Such a low e x p e n d itu r e o f en erg y a llo w s m a in te n a n c e o f s u s t a i n e d c o n t r a c t i o n as t h a t e x h i b i t e d i n a d d u c to r m u scles o f organism s such as clam s. The to n ic 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 o f p a r t i c u l a r im p o rta n c e i n h o llo w v i s c e r a such as th e u r i n a r y b l a d d e r . B o z le r (1 9 2 8 ), p ro p o sed th e id e a t h a t to n u s was due to a s p e c i a l i z e d type o f f i b r i l w it h i n th e c e l l which p roduced t o n i c c o n t r a c t i o n s w h ile a n o th e r ty p e of f i b r i l p r e s e n t w i t h i n th 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 ic k co 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 te d by th 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 th e id e a t h a t t h e r e i s no s p e c i f i c to n ic m echanism , b u t t h a t to n u s co u ld be e x p la in e d by th e slow r e l a x a t i o n of smooth m uscle w hich can be h a s te n e d by a c t i o n o f an 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 to n u s b a se d on o b s e r v a t i o n s of v a r io u s 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 te d by B o z le r (1936) as b e in g due to p e r s i s t e n t , weak 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 ch ro n o u s a c t i v i t y i n d i f f e r e n t p a r t s o f a m uscle* Prom o b s e r v a tio n s o f a c t i o n p o t e n t i a l s , i t was shown t h a t t h e r e i s an i r r e g u l a r d is c h a r g e o f weak im p u lse s c a u s in g i n c o o r d in a te d c o n t r a c t i o n s i n a l l p a r t s . This i n c o o r d i n a t i o n can be e x p la in e d by po o r m uscle c o n d u c tio n r e s u l t i n g i n in d e p e n d e n t d is c h a r g e of many r e g io n s of th e m u s c le . As m en tio n ed p r e v i o u s l y , e x c i t a b i l i t y i n smooth m uscle i s i n f l u e n c e d by horm ones. B o z le r (1 9 4 1 ), by m e a su rin g 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 i l i t y o f th e u t e r u s i n d i f f e r e n t p h a se s of th e s e x u a l c y c l e . D uring a n e s t r u s , m u sc u la r movement was found to be weak and i n c o o r d i n a t e d ; c o n t r a c t i o n s o r i g i n a t e d i n v a r io u s re g io n s and rem ained l o c a l i z e d . F o llo w in g a d m i n i s t r a t i o n of e s t r o n e , e l e c t 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 . L ik ew ise d u r in g e s t r u s , w hich i s c h a r a c t e r i z e d by h ig h e s tr o g e n c o n t e n t , 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 enough, Wbolsey and Me Brooks (1937) found t h a t m i c t u r i t i o n volume d im in is h e d m ark ed ly d u r in g e s t r u s i n c a t s , 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 rtu m . Langworthy and Brack (1939) found t h a t th e u r i n a r y b la d d e r o f p re g n a n t c a t s were c a p a b le o f h o ld in g l a r g e volumes a t low p r e s s u r e s . These r e s u l t s seem to 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 volume i s 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 i s in 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 co n cen t r a t i o n d u r in g p reg n an cy 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 c y c l e . I t h a s been shown t h a t smooth m uscle i s v e ry s e n s i t i v e to a l t e r a t i o n s i n th e h y d ro g e n -io n c o n c e n t r a t i o n . Dixon (1902) d e m o n stra te d t h a t v e ry s m a ll amounts o f l a c t i c a c i d s to p the a u to m a tic waves and p ro d u ce r e l a x a t i o n i n th e smooth m uscle of f r o g stom ach. L.G. Evans (1 9 2 3 ), u sed v a r io u s ty p e s of smooth m uscle to s tu d y th e e f f e c t s of a l t e r a t i o n of pH on th e to n e and c o n t r a c t i o n s . I s o l a t e d s t r i p s of t i s s u e s were su sp e n d ed i n s a l i n e s o l u t i o n and th e pH of th e b a th was a l t e r e d by a d d i t i o n o f a c id s and b a s e s . I n a l l c a s e s , i n c r e a s e d h y d ro g e n - io n c o n c e n t r a t i o n w i t h i n th e l i m i t s of c o m p a t a b i l i t y c au sed r e l a x a t i o n o f to n e of p l a i n m u sc le . A v a r i e t y o f a c i d s were u s e d , and th e e f f e c t s produced by a l l a c id s were th e same. A sudden change to a l k a l i n e pH c au sed an i n c r e a s e i n to n u s . G e llh o rn (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 th e same e f f e c t i s p roduced i n s t r i a t e d m u sc le . I n o r d e r to d e te rm in e w h e th e r th e n erv o u s mechanism m ig h t be r e s p o n s i b l e f o r th e e f f e c t s produced 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 ith n i c o t i n e which a b o l i s h e s b o th m otor and i n h i b i t o r y e f f e c t s o f h y p o g a s tr i c s t i m u l a t i o n , and w ith a t r o p i n e which p a r a l y z e s n e rv e e n d in g s i n smootxi m u sc le . The e f f e c t of pH was e s s e n t i a l l y tn e same i n r e g a r d to to n u s w ith o r w ith o u t p r e - t r e a t m e n t w ith n i c o t i n e or a t r o p i n e . T his seems 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 roduced by a c i d pH i s e f f e c t e d p r i m a r i l y by a c t i o n on th e m u sc u la r t i s s u e i t s e l f . However, Hammett (1921) found t h a t t r e a t i n g r a t duodenum w ith c o c a in e a b o l i s h e d th 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 te and co n c lu d e d t h a t th e e x t r i n s i c n e rv e f i b e r s or e n d in g s i n i n t e s t i n a l segm ents a r e p r i m a r i l y s t i m u l a t e d . No m e n tio n i s made w ith r e s p e c t to r e a c t i o n to a c i d s o l u t i o n s . L i t e r a t u r e on th e p h y s io lo g y of m i c t u r i t i o n . A lthough m ost o f th e l i t e r a t u r e c o n c e rn in g th e p h y s io lo g y o f m i c t u r i t i o n h as been b ased on e x p e r im e n ta l work p erfo rm ed on c a t s , a b r i e f re v ie w of th e s e s t u d i e s seems i n o r d e r and a p p l i c a b l e i n r e l a t i o n to th e p r e s e n t i n v e s t i g a t i o n . S y m p ath etic i n n e r v a t i o n i s d e r iv e d from th e lum bar r e g io n o f th e s p i n a l c o rd from th e seco n d , t h i r d and f o u r t h lum bar se g m e n ts. F ib e r s le a v e the s p i n a l c o rd as th e lum bar s p la n c h n ic n e r v e s , p ass th ro u g h th e g a n g lia of th e s y m p a th e tic 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 ic g a n g l i a . H ere, c e l l s t a t i o n s o c c u r where th e p r e g a n g l i o n ic f i b e r s form s y n a p tic c o n n e c tio n w ith p o s tg a n g l i o n i c f i b e r s which ru n downward as 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 , o r as i t i s sometimes c a l l e d , th e p e l v i c p le x u s . The f i b e r s th en e n t e r th e v e s i c a l p le x u s which l i e s on th e b l a d d e r w a ll and which co n t a i n s c e l l s t a t i o n s f o r p r e g a n g l i o n ic f i b e r s t h a t h ave p a sse d th ro u g h th e i n f e r i o r m e s e n te r ic g a n g lio n . P a ra s y m p a th e tic f i b e r s 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 rd from 13 th e seco n d , 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 th e p e l v i c n e rv e which e n t e r s th e h y p o g a s tr i c p le x u s . S h o rt p o s tg a n g l i o n i c f i b e r s a r i s e i n th e v e s i c a l g a n g lia and p ass to th e body and neck of th e b l a d d e r . The p u d ic n e r v e s , which a r e s o m a tic , i n n e r v a t e th e s t r i a t e d m uscle o f th e com p r e s s o r u r e t h r a e ; th e y a r i s e i n th e s a c r a l r o o t s betw een th e f i r s t and f o u r t h s a c r a l seg m e n ts. L i t e r a t u r e c o n c e rn in g th e f u n c t io n s of n e r v e s i n n e r v a t i n g th e b la d d e r i s c o p io u s b u t i n g e n e r a l , r e p o r t e d o b s e r v a tio n s a r e c o n f l i c t i n g . W hile th e sy m p a th e tic and p a ra s y m p a th e tic n erv o u s system s a r e g e n e r a l l y b e l i 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 i c 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 in g th e s p h i n c t e r and th e p e I v i e s a c t i n g o p p o s i t e l y , many i n v e s t i g a t o r s have r e p o r t e d e x c e p tio n s which a r e n o t i n agreem ent w ith th e th e o ry of a n t a g o n i s t i c a c t i o n . E l l i o t (1 9 0 6 ), 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 th e b la d d e r v a r i e s from one a n im al to a n o th e r and t h a t g e n e r a l i z a t i o n s from 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 ly to o th e r s p e c i e s . He m a in ta in e d t h a t d i f f e r i n g o b s e r v a tio n s were due to a r g u in g from the p a r t i c u l a r to th 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 to cau se g e n e r a l b la d d e r c o n t r a c t i o n . On th e o t h e r h an d , th e e f f e c t o f s ti m u l a t i o n o f th e h y p o g a s tr i c n e rv e s was found to d i f f e r . I n the dog, r a b b i t and man, th e h y p o g a s tr i c s produced c o n t r a c t i o n s o n ly i n a s m a ll a r e a a t th e base of th e b la d d e r c lo s e to th e 14 s p h i n c t e r ; i n th e f e r r e t and th e m ale g o a t, t h e whole b la d d e r c o n t r a c t e d . In th e c a t , p i g , and monkey a g e n e r a l r e l a x a t i o n was n o te d . S te w a rt (1 8 9 9 ), d e s c r i b e d u n i l a t e r a l c o n t r a c t i o n s o f th e b l a d d e r w a ll fo llo w e d by r e l a x a t i o n upon h y p o g a s tr ic s t i m u l a t i o n . Langworthy, R eeves, and Tauber (1934), found d e c re a se d b la d d e r c a p a c i t y a f t e r h y p o g a s tr i c l e s i o n s and c o n clu d ed t h a t th e sy m p a th e tic system i n h i b i t s p a ra s y m p a th e tic a c t i v i t y . Denny-Brown and R o b e rtso n (1933) found norm al b la d d e r f u n c t io n i n human s u b j e c t s f o llo w in g p r e s s e r a i neu recto m y , i n d i c a t i n g no e v id e n c e t h a t th e h y p o g a s tr i c n e rv e s p la y any p a r t i n b la d d e r i n n e r v a t i o n . The v a l i d i t y o f s t u d i e s em ploying methods o f d i r e c t f a r a d i z a t i o n o f n e rv e f i b e r s a s a b a s i s o f co m parison f o r norm al e f f e c t s h as been q u e s tio n e d by MacDonald and McCrea (1 9 3 0 ). They r e p o r t e d t h a t th e e f f e c t o f any g iv e n s tim u lu s v a r i e s w ith th e e x i s t i n g c o n d i t i o n o f th e v i s c u s . The e f f e c t produced was found to v a ry n o t o n ly w ith th e s t r e n g t h o f th 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 stu d y o f a c t i o n c u r r e n t o f n e rv e s s u p p ly in g th e u r i n a r y b l a d d e r . The r e s u l t s he o b ta in e d showed t h a t th e v e s i c a l p le x u s a c t i v i t y f o llo w in g s e c t i o n i n g of th e p e l v i c s was c o m p le te ly l a c k in g ; fo llo w in g s e c t i o n i n g o f th e h y p o g a s t r i e s , no change was n o te d . T a la a t (1 9 3 7 ), r e p o r t e d a f f e r e n t im p u lse s were o b ta in e d from th e h y p o g a s tr ic 15 n e rv e a f t e r p e l v i c n e rv e d e g e n e r a t i o n . These d i s c h a r g e s were found to d i s a p p e a r a f t e r i s o l a t i n g th e b l a d d e r . T a la a t su g g e s te d t h a t th e s e im p u lse s had 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 and t h a t d is c h a r g e from th e h y p o g a s tr ic n e rv e was due l a r g e l y to p e l v i c f i b e r s mixed w ith h y p o g a s tr i c f i b e r s . This has b een d e m o n stra te d a n a t o m i c a l l y by Langworthy (1 9 3 9 ). C u ttin g th e h y p o g a s t r i c s a b o lis h e d th e r i s e i n b lo o d p r e s s u r 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 , w h ile c u t t i n g th e p e l v i c s d id n o t . T h is , was i n t e r p r e t e d as i n d i c a t i n g th e p r o b a b i l i t y t h a t th e f u n c t i o n of a f f e r e n t f i b e r s i n th e hypo g a s t r i c n e r v e s i s to c a r r y p a i n f u l im p u lse s to th e c e n t r a l n e rv o u s sy stem . Prom th e e v id e n c e p r e s e n t e d , i t would seem t h a t th e h y p o g a s t r i c s p la y l i t t l e or no p a r t i n m i c t u r i t i o n . The q u e s ti o n a r i s e s as to w h e th e r th e sy m p a th e tic n e rv e s a c t u a l l y i n n e r v a t e th e d e t r u s o r m uscle o r w h eth er th e blood v e s s e l s a lo n e a r e i n n e r v a t e d . To answ er t h i s q u e s t i o n , h i s t o l o g i c a l i n v e s t i g a t i o n s have been made and th e s e a g a in a r e n o t i n a g reem en t. Langworthy and Murphy (1939) made a s tu d y of the n e rv e en d in g s i n th e v i s c u s and o b serv ed th e ty p e s l o s t a f t e r d i f f e r e n t i a l n e rv 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 t e c h n iq u e . The m a j o r i t y o f n e r v e s were found to o c c u r on th e b lood v e s s e l s o f th e b la d d e r and th e y t h e r e f o r e co n clu d ed t h a t th e sy m p a th e tic i n f l u e n c e i s m e d ia te d by changes i n c o n t r a c t i o n s o f th e smooth m u s c u la tu re o f th e b lo o d v e s s e l w a lls and n o t 16 by d i r e c t i n n e r v a t i o n of th e d e t r u s o r m uscle i t s e l f . On th e o t h e r h a n d , Kuntz and Saccomanno (1944) u s in g th e O a ja l s i l v e r te c h n iq u e n o te d d i f f e r e n t i a l s t a i n i n g of s y m p a th e tic and p a ra s y m p a th e tic 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 c lu d e d t h a t f u n c t i o n a l s y m p a th e tic 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 does o c c u r. More c o n c lu s iv e d a t a c o n c e rn in g m i c t u r i t i o n have been o b ta in e d by th e employment o f more n a t u r a l s t i m u l i . B a r r in g to n (1914-1941) i n a s e r i e s of p a p e rs made a s tu 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 o f th e n erv o u s sy stem , he n o te d th e l e v e l i n th e c e n t r a l n erv o u s 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 , th e p a r t s 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 t u r i t i o n to ta k e p l a c e , and th e sim p le r e f l e x components o f m i c t u r i t i o n a lo n g w ith r e f l e x c e n t e r s and p a t h s . I n o r d e r to d e te rm in e th e e f f e c t s o f v a r io u s d e s e n s i t i z i n g m ethods on m i c t u r i t i o n , e x p e rim e n ts were perform ed on d e c e r e b r a t e c a t s , 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 , o r e t h e r . The b la d d e r was em ptied by p a s s in g a c a t h e t e r th ro u g h th e u r e t h r a i n t o th e v i s c u s . When f l u i d f i r s t a p p e a re d a b o u t th e u r e t h r a l p o r t i o n e n c lo s in g th e c a t h e t e r , th e c a t h e t e r was removed from th e u r e t h r a and th e volume e li m i n a t e d was m easu red . I t was found t h a t th e volume e lim i n a t e d by d e c e r e b r a t e c a t s was g e n e r a l l y s l i g h t l y low er th a n th e volume e l i m i n a t e d by norm al c a t s . While th e fre 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 found to be s l i g h t l y g r e a t e r th an i n norm al a n im a ls ; th 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 , e l i m i n a t i o n was found to be co m plete i n d e c e r e b r a t e c a t s , i n d i c a t i n g t h a t norm al r e f l e x m i c t u r i t i o n may ta k e p la c e i n the a b se n c e o f th e f o r e b r a i n . The b l a d d e r volume i n c a t s a n e s t h e t i z e d w ith e t h e r and c h lo ro fo rm was g e n e r a l l y g r e a t e r th a n i n d e c e r e b r a t e a n im a ls , and th e s e a n e s t h e t i c s were found to have 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 Langworthy (1938) found 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 and n em butal on th e m i c t u r i t i o n r e f l e x and co n clu d ed t h a t t h e s e a n e s t h e t i c s 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 a c t i v e v e s i c a l c o n t r a c t i o n . D e c e re b ra te c a t s were u sed to a n a ly 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 se d th ro u g h th e u r e t h r a i n t o th e b la d d e r and th e b la d d e r was d i s t e n d e d w ith warm w a te r from a b u r e t t e . I n te r p o s e d betw een th e b u r e t t e and th e c a t h e t e r was a v e r t i c a l tu b e used as a w a te r m anom eter. E qual volumes o f w a te r were ru n i n t o th e b la d d e r e v e ry o t h e r m in u te and p r e s s u r e s were n o te d a t th e end o f one m in u te a f t e r each i n c r e a s e i n volum e. When a c e r t a i n volume was r e a c h e d , w a te r e sc a p e d . T his volume was f a i r l y c o n s i s t e n t i n th e same c a t . I n c r e a s e s i n p r e s s u r e p roduced 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 o f th e t o l e r a t i o n volume were n o t g r e a t s in c e th e b la d d e r had tim e to a d a p t i t s e l f . However, when th e l i m i t was r e a c h e d , th e p r e s s u r e ro s e i n a few seconds to f i f t e e n tim es i t s p re v io u s v a lu e , due 18 to a c t i v e c o n t r a c t i o n s of the b l a d d e r . I n a p e r f e c t l y e l a s t i c bag, a g iv e n in c re m e n t when th e bag i s d is te n d e d r e s u l t s i n a l a r g e r p r e s s u r e i n c r e a s e th a n when th e bag i s l a x ; b u t th e p r e s s u r e i n c r e a s e i s n o t 200-1400^ o v er th e 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 th e c ase i n th e u r i n a r y b l a d d e r . The s tim u lu s p ro d u c in g c o n t r a c t i o n of th e b la d d e r was a c t i v e d i s t e n s i o n o f th e b l a d d e r w a l l , s in c e i n t r o d u c t i o n o f s m a l l e r volumes a t s h o r t e r i n t e r v a l s , n o t a llo w in g th e b la d d e r to become a d a p te d , was e f f e c t i v e i n ev o k in g a c t i v e c o n t r a c t i o n s o f th e v e s i c a l m u s c u la tu r e . I t was n o te d t h a t i f th e b la d d e r were p r e v i o u s l y f i l l e d w ith c o c a in e h y d r o c h lo r id e and th e n d i s t e n d e d w ith w a te 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 limb o f th e r e f l e x a rc a r i s e s i n th e v e s i c a l w a ll and t h a t a b o l i t i o n of th e r e f l e x was due to d e s e n s i t i z a t i o n of the s e n s o ry mechanism by c o c a in e . T his f i r s t r e f l e x i n th e a c t o f m i c t u r i t i o n was found to be d e s tr o y e d a f t e r d i v i s i o n o f th e p e l v i c n e r v e s , or a f t e r 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 low er t h o r a c i c o r u p p e r c e r v i c a l r e g io 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 n erv o u s sy stem . The r e f l e x c e n t e r , t h e r e f o r e , was c o n clu d ed to la y i n th e r e g i o n o f th e h in d b r a i n , w ith p a th s 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 l v i c n e r v e s . B a r r in g to n l o c a l i z e d th e c e n t e r by making t r a n s e c t i o n s b eh in d a p la n e th ro u g h th e p o s t e r i o r p a r t s o f 19 th e i n f e r i o r c o l l i c 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 t e r i o r s u r f a c e o p p o s ite th e c e r e b r a l p e d u n c le s ) and th e m id d le o f th e pons v e n t r a l l y . I n th e m id -p o n tin e t r a n s e c t i o n , t h e r e r e s u l t e d a lo s s o f th e r e f l e x , t h e r e f o r e he co n c lu d e d t h a t t h i s a r e a i s th e h i g h e r r e f l e x c e n t e r . The p a th s s u b s e r v in g m i c t u r i t i o n were shown by p a r t i a l s e c t i o n s a t v a r io u s l e v e l s to be i n th e d o r s a l h a l f o f th e l a t e r a l column n e a r i t s p e r i p h e r y . A c tiv e c o n t r a c t i o n of th e b la d d e r was n o te d when the c a t h e t e r was moved i n th e u r e t h r a . I n o r d e r to check th e p o s s i b i l i t y 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 th e u r e t h r a l w a l l , a n o t h e r method was u s e d . Tiie b la d d e r n eck was d iv id e d p ro x im a l to where th e u r e t h r a b e g in s to expand and two c a n n u la e , one i n each c u t end, were t i e d , a llo w in g s im u lta n e o u s o b s e r v a t i o n o f b la 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 tu b e s w ith a T -tu b e f i t t e d a t th e low er end were used as w a te r m anom eters. One end o f th e T -tu b e was c o n n e c te d to th e c a n n u la w h ile th e o t h e r end v/as c o n n e c te d to a f i l l i n g b u r e t t e . P r e s s u r e s c o u ld be re a d when th e clamp to th 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 below t h a t n e c e s s a r y to produce r e f l e x c o n t r a c t i o n and th e u r e t h r a l p r e s s u r e was r a i s e d 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 . I t was found t h a t when w a te r esc a p e d from th e e x t e r n a l m e a tu s, p o w e rfu l c o n t r a c t i o n s o f th e b la d d e r o c c u rre d p ro d u c in g a r i s e i n p r e s s u r e e q u a l to t h a t p roduced by b l a d d e r d i s t e n s i o n 20 i n th e f i r s t r e f l e x . The p r e s s u r e rem ained u n t i l th e w a te r no lo n g e r e sc a p e d . The r e f l e x co u ld s t i l l be o b ta in e d a f t e r c o c a in e had been a p p l i e d to th e i n t e r i o r b la d d e r w a ll show in g t h a t t h i s second r e f l e x c o n t r a c t i o n o f th e b l a d d e r was n o t i n i t i a t e d by th e same s tim u lu s as t h a t f o r th e f i r s t . The r e f l e x was d e s tr o y e d by d i v i s i o n of th e p e l v i c n e r v e s , th e p u d ic s and by t r a n s e c t i o n of th e s p i n a l co rd i n th e low er t h o r a c i c or u p p er c e r v i c a l r e g i o n s . Thus, th e e f f e r e n t p a th v/as co n clu d ed to be i n th e p e l v i c s , th e a f f e r e n t i n th e p u d ic s 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 . I t i s i n t e r e s t i n g to n o te t h a t T a la a t (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 im p u lse s o f n e r v e s s u p p ly in g th e b la 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 th ro u g h th e u r e t h r a was e f f e c t i v e i n s t i m u l a t i n g s e n so ry n e rv e e n d in g s i n th e u r e t h r a . D is c h a rg e o f a f f e r e n t im p u lse s v/as n o te d i n th e p u d ic n e rv e o n ly , and th e d is c h a r g e co u ld be m a in ta in e d by th e flo w a t low er p r e s s u r e s th an were n e c e s s a r y to evoke a c o n tin u o u s d is c h a r g e due to 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 ib e d as b e in g due to d i s te n s i o n o f th e p o s t e r i o r r e g i o n o f th e u r e t h r a , s in c e r i s 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 rre d when th e p r e s s u r e i n th 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 to f o r c e th e s p h i n c t e r . I t was n o te d t h a t when th e u r e t h r a l p r e s s u r e re a c h e d 30 cm. o f w a te r i t f e l l l / 2 cm. o f w a te r w ith a s u b se q u e n t t r a n s i t o r y r i s e i n b l a d d e r p r e s s u r e . Water d id n o t e s c a p e , how ever, u n t i l 50 cm. w a te r p r e s s u r e . The r e f l e x was d e s tr o y e d only 21 by d i v i d i n g th e h y p o g a s tr i c s and was n o t a f f e c t e d by d i v i s i o n of th e s p i n a l cord as i n th e f i r s t two r e f l e x e s . The f o u r t h r e f l e x e l i c l L e d by w a te r ru n n in g th ro u g h th e u r e t h r a was o b se rv e d v/hen a d d in g w a te r to th e u r e t h r a l manometer a t th e r a t e of 5 cm. p e r m in u te . W ater escap ed v/hen th e p r e s s u r e was r a i s e d to 34 cm. o f w a te r and sto p p e d when th e p r e s s u r e f e l l to 10 cm. o f w a te 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 betw een 10 cm. o f w a te r and 35 cm. of w a te r when f l u i d was n o t ru n n in g th ro u g h , b u t t h e r e was no r e s i s t a n c e when w a te r was e s c a p in g . T his r e f l e x th en c o u ld be e x p la in e d as b e in g due to r e f l e x r e l a x a t i o n of u r e t h r a l m u scles and v/as s t i m u l a t e d by ru n n in g w a te r . I t c o u ld be a b o lis h e d o n ly by d i v i s i o n o f th e p u d ic s . I f th e u r e t h r a l manometer were f i l l e d to a b o u t one h a l f th e p r e s s u r e n e c e s s a r y to s t a r t e sc a p e , betw een 10-35 cm. o f w a te r , and th e b la d d e r were d is te n d e d v i a th e o t h e r c a n 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 cau sed e scap e of w a te 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 of th e u r e t h r a . The r e f l e x was d e s tr o y e d only by d i v i s i o n o f th e p e l v i c s . T ra n s e c t i o n o f th e s p i n a l co rd e f f e c t e d th e r e f l e x o n ly th ro u g h i t s i n f l u e n c e on th e b la 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 shov/n t h a t i f th e b l a d d e r were d is te n d e d s u f f i c i e n t l y a f t e r t r a n s e c t i o n , u r e t h r a l d i l a t a t i o n c o u ld s t i l l ta k e p l a c e . I t was, t h e r e f o r e , con clu d ed t h a t a f i f t h r e f l e x e x i s t s , th e r e f l e x c e n t e r b e in g i n th e s p i n a l co rd w ith th e 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 a r r in g to n (1931) n o te d t h a t i f th e p e lv ic n e rv e s were c u t i n a c a t , i n which th e s p i n a l co rd n e a r th e l e v e l of 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 , t h e r e r e s u l t e d an i n c r e a s e i n th e volume of r e s i d u a l u r i n e . This su g g e ste d a n o th e r s p i n a l r e f l e x th e s i x t h , h a v in g b o th p a th s 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 of th e u r e t h r a o r 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 th er method was u sed to m easure i n c r e a s e d r e s i s t a n c e o f th e u r e t h r a . The s p i n a l cord was t r a n s e c t e d i n th e l a s t t h o r a c i c o r f i r s t lumbar segments and th e i n f e r i o r g a n g lia were e x c is e d u n d e r c h lo ro fo rm and e t h e r . A f t e r t h r e e w eeks, th e p u d ic n e rv e s were d iv id e d and th e p e l v i c s were ex p o sed . A c a n n u la was t i e d to th e fundus o f th e b l a 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 lo ro fo rm and a f t e r an i n t e r v a l th e b l a d d e r was em p tied by a c a n n u la and w a te r was th e n i n t r o d u c e d . The minimum p r e s s u r e which gave r i s e to e sc a p e was n o te d . Thus he c o n clu d ed t h a t t h e r e must be a n o th e r s p i n a l r e f l e x th e s i x t h h a v in g b o th p a th s i n th e 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 o f th e 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 . I n i n v e s t i g a t i n g th e second r e f l e x i t was n o t i c e d t h a t i n some e x p e rim e n ts b la d d e r c o n t r a c t i o n s o c c u rre d v/hile ru n n in g w a te r th ro u g h th e u r e t h r a a f t e r th e pudic n e rv e s had been c u t . I n th o se c a s e s where c o n t r a c t i o n s sto p p e d a f t e r c u t t i n g th e p u d ic s , c o n t r a c t i o n s c o u ld be e l i c i t e d by i n j e c t i n g 23 w a te r r a p i d l y i n t o th e u r e t h r a , Ttie r e f l e x was a b o lis h e d by d i v i s i o n of th e p e l v i c n e r v e s , Vihile t h i s s e v e n th r e f l e x co u ld be d e s tr o y e d by d i v i s i o n of b ra n c h e s o f th e p e l v i c p le x u s to th e u r e t h r a , the second c o u ld n o t . The mean r a t e o f flow n e c e s s a r y to e l i c i t th e se v e n th was found to be 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 th e seco n d . A summary o f B a r r in g to n * s breakdown of r e f l e x e s in v o lv e d i n m i c t u r i t i o n i s p r e s e n t e d i n Table I . A nother method of 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 tro d u c e d by Denny-Brown and R o b e rtso n (1 9 3 3 ), i n an e x t e n s iv e s tu d y p erfo rm ed on human s u b j e c t s . A u n iq u e system o f do u b le c a t h e t e r s 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 and th ro u g h t h i s was p a s se d a c a t h e t e r o f s m a lle r o u t s i d e d ia m e te r to r e c o r d v e s i c a l p r e s s u r e . By m a n ip u la tio n o f th e c a t h e t e r s , v a r io u s p o r t i o n s co u ld be o b serv ed s im u lta n e o u s ly . The two c a t h e t e r s were c o n n e c te d to two manometers on which were mounted 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 photokym ograph. Three o t h e r manometers were u se d to r e c o r d s im u lta n e o u s ly abdom inal movements, p r e s s u r e in th e rectu m , and movements o f th e perineum , p r e s e n t i n g a p i c t u r e of th e a c t u a l b la d d e r and u r e t h r a l a c t i v i t y a lo n g w ith se c o n d a ry o r s u p p le m e n ta ry a c t i v i t y . I § o a a a u m l c • H • H O J U •H ■ E o Ü m J k o o ■ s o o m J o o t o o 24 < 0 0 C O C O o P P i 0 0 C O 0 9 O l i p © p P o © p o o • H © P i o p p 0 3 p • H > © p P > > d m 3 m 3 P / d o o p p b O d d © © p is H © © o P i P i P i d > s g 1 A A 1 d P P © r © P i M a o M E H H p :; g O H 0 m 1 E H M is; O fU g o o M g K © P Ü < C O * H P L i c C O P i 0 0 • H o p Ü P > • H w p p m 3 d p © d b O d ft ft O ft N ft k < © © © p p P P P P o o o o o o w C O © d d d d d d o s o s o g d d P p p • H O P i q p P i p P i P P i p c d M o o o o Ü O p p P i d w d O T d 0 0 d © P i P i d d d P i d % d H p P i p P i p P i d d d p d p d p p o © o © o © © p o m 3 O p o P c d o C Û 3 != ) S 5 o] < H o H iH Ü aj O & •H C O C h C (D < D 7j -p m j W 0 3 * H iH P rQ OS P n ( D -P -P C D i ^ g'-â •H 0 I I O g * H O U •tH (D C O -P c d C O ^ ( D O ^ ■ P A P C O ( D P 4n P - I p o d d ? H ^ ® P p ® % 0 S’-a p p { l l 0 0 o •pH > H ® A P J d o ^ P P d ® W fn a ^ < D P 0:: o o o p P 4 C O < D 0 m j ® m J P d 0 3 f I *rH m m j C O o P > P ® cu q d o P i P r C P P d ® s s ® p D :; O Ü ÎH o ® p m J 0 0 q d ® p C O P g 03 O d P ® iH 03 Pn © Æ O g > d P P i © r O P4 © P P o o 03 P Î O • H P O % P i o d C O P i d o © 0 m d d P i p © 1 d “ I ’ I I H o :: H P H P P > P P > P > CHAPTER I I I EXPERIMENTAL DATA M a t e r i a l s and m e th o d s. I n o r d e r to c a n n u l a t e th e i n t a c t u r i n a r y b l a d d e r of th e 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 c o n c o m ita n t w ith th e i n t r o d u c t i o n o f p e r f u s a t e s i n t o th e b l a d d e r , some ty p e o f d e s e u s i t i z a t i o n m ust be employed which does n o t i n t e r f e r w ith norm al m i c t u r i t i o n . E th e r and n em b u tal 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 . I n r a t s a n e s t h e t i z e d w ith e t h e r , t h e r e i s no r e t e n t i o n of i n j e c t e d p e r f u s a t e , b u t r a t h e r a l o s s o f f l u i d th ro u g h th e u r e t h r a w ith each i n t r o d u c t i o n o f s o l u t i o n i n t o th e b l a 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 n em b u tal a n e s t h e s i a , th e b l a d d e r p r e s s u r e r i s e s s t e a d i l y w ith i n c r e a s i n g volum es, w ith l i t t l e o r no r e l a x a t i o n o f th e m u s c u la tu r e . T erm in al p a s s iv e d i s t e n s i o n , which n o rm a lly evokes a c t i v e c o n t r a c t i o n s o f th e d e t r u s o r m u scle 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 c a u se s o n ly a s l i g h t l o s s 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 g r e a t enough to p a s s i v e l y f o r c e f l u i d th ro u g h th e u r e t h r a . Nembutal th u s seems to d e p re s s 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 t a i n 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 la d d e r em ptying and norm al m i c t u r i t i o n . Kolb and Langworthy (1938) n o te d s i m i l a r e f f e c t s i n c a t s . A n o th er f a c t o r w hich makes th e use o f n em b u tal u n d e s i r a b l e i s th e v a r i a b i l i t y o f d e p th o f a n e s t h e s i a . U n less means a r e p ro v id e d to i n s u r e c o n s t a n t d e p th 26 o f a n e s t h e s i a , b la d d e r a c t i v i t y i s v a r i a b l e , and t h i s makes im p o s s ib le , th e d isc e rn m e n t of v a r i a b i l i t y of a c t i v i t y i n r e a c t i o n to v a r io u s p e r f u s a t e s . As d is c u s s e d i n th e p r e v io 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 t e c a t s i n which th e f o r e b r a i n h as b een 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 an a tte m p t to stu d y th e e f f e c t o f th e pH o f p e r f u s a t e s on v e s i c a l a c t i v i t y and th e norm al a c t o f m i c t u r i t i o n , d e c e r e b r a t i o n of a n im als would th e n seem to be th e i d e a l method o f d e s e n s i t i z a t i o n . D e c e r e b r a tio n i s a c c o m p lish e d by d i v i d i n g th e n erv o u s a x is a t th e l e v e l o f th e m i d - b r a i n . D e s t r u c t i o n o f a l l p a r t s a n t e r i o r to th e s e c t i o n r e s u l t s , and body f u n c t i o n th e n rem ain s u n d e r c o n t r o l o f th e p o n s, m e d u lla , 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 s e r v e d , so such a p r e p a r a t i o n i s q u i t s s u i t a b l e f o r a s tu d y o f r e f l e x m i c t u r i t i o n . D e c e r e b r a te r a t s , how ever, were found to be q u i t e d i f f i c u l t to p r e p a r e , and a v e ry low p e r c e n ta g e of th e a tte m p te d o p e r a t i o n s were s u c c e s s f u l . The v a r io u s m ethods a tte m p te d and r e s u l t s 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 , th e tr a c h e a was exposed and a c a n n u la was i n s e r t e d and t i e d i n . The s lru ll bones were e x posed by d o r s a l m i d - l i n e s k in i n c i s i o n . The p a r i e t a l bones were sawed a n t e r i o r to th e t r a n s v e r s e s i n u s . Bone f o r c e p s and a d e n t a l d r i l l were u se d to f r e e th e bone a lo n g th e l a t e r a l 27 r id g e s o f th e c ran iu m . The h e m isp h e re s were exposed and c a r e f u l l y scooped o u t. The c a v i t y was packed w ith c o t t o n . This i s a m o d i f i c a t i o n of th e method d e s c r ib e d by L andis (1 9 3 0 ). A g r e a t amount of hem orrhage o c c u rre d from th e bone s in u s e s as a r e s u l t o f saw ing. A f t e r th e s k u l l had been p e n e t r a t e d , e x 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 rem oval o f th e c e r e b r a l h e m is p h e re s , th e an im al showed s ig n s o f d im in ish e d r e s p i r a t o r y movements and w ith in a few m in u te s r e s p i r a t i o n sto p p e d c o m p le te ly . A p p l i c a t i o n of 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 o f th e a n im a l. Tliis method 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 , th e r e s p i r a t o r y c e n t e r was im m e d ia te ly i n j u r e d , p o s s i b l y due to t r a c t i o n cau sed by l i f t i n g o u t th e c e r e b r a l h e m isp h e re s . Trauma produced by saw ing th e s k u l l , and shock r e s u l t i n g from e x c e s s iv e hem orrhage may a l s o h ave c o n t r i b u t e d to d e a t h . I n one c a s e , a m ix tu re o f b lo o d c l o t and mucus was found i n the 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 , r e s p i r a t o r y f a i l u r e may have been due to an o cclu d ed a i r p a s s a g e . I I . Under 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 la was i n s e r t e d by ex p o sin g th e a r e a i n th e n eck r e g i o n . The s k u l l was exposed by a s k in i n c i s i o n , th e p a r i e t a l bones were sawed a n t e r i o r 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 isp h e re s were p a r t i a l l y ex p o sed . An ethm oid c u r e t t e was p a sse d downward to th e f l o o r o f th e s k u l l a t th e l e v e l of th e p o s t e r i o r r e g io n o f th e cerebrum and by moving th e in s tr u m e n t 28 l a t e r a l l y a com p lete t r a n s e c t i o n was acco m p lish e d . U sing t h i s m ethod, 3 d e c e r e b r a t e r a t s were o b ta in e d w ith a f a i r l y lo n g s u r v i v a l p e r i o d . Normal r e s p i r a t o r y movements were m a in ta in e d a f t e r th e t r a n s e c t i o n i n th e s e 3 c a s e s . I n one a n im 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 re d 15 m in u te s a f t e r t r a n s e c t i o n , b u t i t was r e v iv e d by a r t i f i c i a l r e s p i r a t i o n . A g r e a t amount o f hem orrhage o c c u rre d w h ile e x p o sin g th e cereb ru m , b u t t h i s was sto p p e d by p ac k in g w ith c o t t o n . Two o f t h e s e an im a ls l i v e d 3 h o u r s ; th e o t h e r r a t was k i l l e d 6 h o u rs a f t e r d e c e r e b r a t i o n . H aving s u c c e s s f u l l y p roduced 3 s u c c e s s iv e d e c e r e b r a t e a n im a ls , th e same method was a tte m p te d on 10 o r more r a t s w ith co m plete f a i l u r e . U sing a p p a r e n t l y th e same te c h n iq u e , th e b r a i n was t r a n s e c t e d i n th e same r e g i o n . A f t e r 16 to 30 m in u te s 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 . A ttem p ted r e s u s c a t a t i o n u s in g 95^ Ü2 and b% COg gas m ix tu re was in a d e q u a te i n r e v i v i n g th e a n im a l. I t was th o u g h t t h a t p e rh a p s th e t r a c h e a l c a n n u la was b e in g o cclu d ed by mucus so s e v e r a l a tte m p ts were made e l i m i n a t i n g th e use of th e c a n n u la . In 1 o r 2 c a s e s t h i s d id seem to p r o lo n g th e a n im a le s l i f e , b u t o p e r a tio n s were n o t c o n s i s t e n t l y s u c c e s s f u l . P o st mortem e x a m in a tio n d id n o t r e v e a l any a p p a r e n t damage to th e m ed u lla o r pons r e g i o n s . The r e a s o n f o r th e g r e a t number of f a i l u r e s c o u ld n o t be d e te rm in e d . I t was th o u g h t t h a t p erh a p s th e g r e a t l o s s o f b lo o d r a t h e r th a n r e s p i r a t o r y f a i l u r e was th e prim e r e a s o n . 29 I I I . To e l i m i n a t e th e hem orrhage f a c t o r , d é c é r é b r a t i o n was a tte m p te d a f t e r i n s e r t i n g a c a n n u la i n th e exposed tra c h e a and th e n l i g a t i n g th e c a r o t i d a r t e r i e s (u n d er e t h e r a n e s t h e s i a ) . The s k u l l was th e n exposed, and th e p a r i e t a l bones were sawed im m e d ia te ly a n t e r i o r to th e t r a n s v e r s e s i n u s . The m id - b r a in was t r a n s e c t e d u s in g an ethm oid c u r e t t e . Im m e d ia te ly a f t e r t r a n s e c t i o n , th e a n im a l d i e d . T h is method was t r i e d o n ly once. The re a s o n f o r d e a th v/as n o t d e te rm in e d . P o s s i b l y th e e x c e ss traum a produced by e x c e s s iv e h a n d lin g of th e an im al i n th e 3 s u c c e s s iv e s te p s of p r e p a r a t i o n was an im p o rta n t f a c t o r . IV. Under e t h e r a n e s t h e s i a , th e s k u l l was exposed by 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 , a h o le was d r i l l e d i n th e l e f t p a r i e t a l bone a n t e r i o r to th e t r a n s v e r s e s in u s and l a t e r a l to th e l o n g i t u d i n a l s i n u s . Hemorrhage v/as s l i g h t . A p i t h i n g n e e d le v/as p a s se d a t a b o u t a 45^ a n g le to th e r i g h t - h a n d s i d e , v e n t r a l to th e t r a n s v e r s e s in u s and l o n g i t u d i n a l s i n u s . T r a n s e c tio n was a c co m p lish e d by draw ing th e n e e d le a c r o s s th e f l o o r of th e s k u l l to the p la c e o f i n s e r t i o n . The s l i g h t hem orrhage t h a t o c c u rre d was s to p p e d by p a c k in g th e s m a ll h o le w ith c o t t o n . The f i r s t a n im a l l i v e d a p p ro x im a te ly i j h o u r s . The second an im a l l i v e d a p p ro x im a te ly 1 h o u r . The t h i r d an im al d ie d i h o u r a f t e r t r a n s e c t i o n . Viliile im m ediate r e s p i r a t o r y f a i l u r e d id n o t o c c u r, 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 te f o r th e p u rp o se s of e x p e r im e n ta tio n , s in c e 30 a t l e a s t 3 o r 4 h o u rs was r e q u i r e d to a c co m p lish a s e r i e s o f r e c o r d i n g s . P o st mortems r e v e a le d no i n j u r y to th e pons o r m e d u lla . Under n em butal 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 eig h t 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 bones were exposed and d e c e r e b r a t i o n was perform ed u s in g th e same te c h n iq 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 butal 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 had been u n d e r a n e s t h e s i a a p p ro x im a te ly 2^ h o u rs d u rin g which tim e an a d d i t i o n a l .05 c c . was i n j e c t e d d i r e c t l y i n t o th e p e r i t o n e a l c a v i t y th ro u g h th e i n c i s i o n used to expose th e u r i n a r y b l a d d e r . The r a t l i v e d 3j- h o u rs a f t e r d e c e r e b r a t i o n . The second r a t had b een u n d e r a n e s t h e s i a a p p ro x im a te ly 2% h o u rs i n which tim e .05 c c . was i n j e c t e d i n th e same m anner. This 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 , r e s p i r a t o r y f a i l u r e o c c u rre d im m e d ia te ly 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 of a r t i f i c i a l r e s p i r a t i o n , th e an im a ls 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 e c e r e b r a t e p r e p a r a t i o n s were o b ta in e d h a v in g lo n g s u r v i v a l . This same method of d e c e r e b r a t i o n was l a t e r a tte m p te d on a number o f r a t s . The a v e ra g e s u r v i v a l p e r io d was 35 m in u te s f o r th e f i r s t 3 r a t s . B e lie v in g th e n em butal to have to x ic e f f e c t s , 3 u n o p e ra te d c o n t r o l s were ru n u s in g th e same d o sag e, 40 mg/kgm. body w e ig h t. A l l 3 r a t s r e c o v e re d from th e a n e s t h e s i a w ith no i l l 31 e f f e c t s . The f o u r t h d e c e r e b r a t e r a t s u rv iv e d 6 h o u rs a f t e r th e o p e r a t i o n ; th e s u r v i v a l p e r io d f o r th e n e x t 3, how ever, av e ra g e d 60 m in u te s . S in c e mucus f o rm a tio n was n o te d i n m ost c a s e s , a t r o p i n e was a d m in is te r e d to th e n e x t 2 a n im als i n an a tte m p t to e l i m i n a t e r e s p i r a t o r y d i f f i c u l t y d u r in g th e c r i t i c a l p e r io d im m e d ia te ly f o llo w in g t r a n s e c t i o n . The a n im als l i v e d 50 m in u te 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 tte m p t was made u s in g a t r a c h e a l c a n n u la and e t h e r a n e s t h e s i a . The a n im al d ie d a f t e r 1 h o u r. O b v io u sly , r e s u l t s of a l l th e d e c e r e b r a t i o n p ro c e d u re s d e s c r i b e d above were a m a t t e r o f chance i n which no p r e d i c t i o n c o u ld be made i n r e g a r d to s u r v i v a l p e r i o d . Such p ro c e d u re s were e x tre m e ly c o s t l y i n tim e as w e ll as i n e x p e r im e n ta l a n im a ls , s in c e a l l t o t a l e d , th e r e was a p p r o x im a te ly an 88% m o r t a l i t y . Two d i f f e r e n t m ethods were found i n th e l i t e r a t u r e which p r e v i o u s l y had n o t been t r i e d . Windl e and M inear (1 9 3 3 ), d e s c r i b e d an anemia 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 in 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 ro a c h . However, i t was n o t found n e c e s s a r y to use t h i s method s in c e an e x c e l l e n t te c h n iq u e v ery r e c e n t l y d ev elo p ed by A nderson and Haymaker (1 9 4 9 ), proved v e ry e f f e c t i v e and v e ry sim p le w ith a low p e r c e n ta g e m o r t a l i t y . With s l i g h t m o d i f i c a t i o n s , th e method d e s c r i b e d was as f o llo w s : V. H ats were a n e s t h e t i z e d w ith n e m b u ta l; th e d o sag e, 2 .5 m g ./ 100 gm. body w e ig h t, was 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 . 32 P re c e d in g th e o p e r a t i o n , .05 c c . c alciu m g lu c o n a te /lO O gm. body w eig h t was a d m in is te r e d i n t r a m u s c u l a r l y to f a c i l i t a t e c l o t t i n g , ( th e c o n c e n t r a t i o n was 1% made up i n i s o t o n i c s o l u t i o n ) . Im m e d ia te ly b e f o r e making th e s k in i n c i s i o n , th e s c a l p was i n f i l t r a t e d w ith a p p ro x im a te ly 0 .4 c c . 2% p ro c a in 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 , 2 h o l e s were d r i l l e d i n th e p a r i e t a l bones im m e d ia te ly a n t e r i o r to th e t r a n s v e r s e s in u s n e a r th e l a t e r a l r i d g e s of th e cran iu m . Then u s in g bone f o r c e p s , th e s k u l l was c u t m e d ia lly from th e h o le s im m e d ia te ly a n t e r i o r to th e t r a n s v e r s e s i n u s , and a n t e r i o r l y , a b o u t 4 mm. a lo n g th e l a t e r a l r i d g e s . The bone was l i f t e d and th e p o s t e r i o r r e g io n o f th e cerebrum was th u s ex p o se d . S u c tio n , u s in g a w a te r a s p i r a t o r and a f i n e p i p e t t e was employed to remove s m a ll 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 th e m i d - b r a i n was p ro d u ced , and th e f l o o r o f th e s k u l l was c o m p le te ly 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 le was l o o s e l y packed w ith c o t t o n soaked i n c a lc iu m g lu c o n a te s o l u t i o n , and th e s k in i n c i s i o n v/as c lo s e d w ith 3 o r 4 s u t u r e s . The a n im a ls were k e p t in c u b a te d u n d e r a lam p, a t a te m p e ra tu re o f a p p ro x im a te ly 27° C . , and th e r e c t a l te m p e ra tu re was m a in ta in e d a t a p p ro x im a te ly 3 3 ° -3 4 ° C. In t h i s m a t t e r , the d e c e r e b r a t e r a t s were k e p t 8-24 h o u rs u n t i l re a d y f o r use i n m i c t u r i t i o n e x p e rim e n ts . 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 re d . The s u r v i v a l p e r io d was 11-45 h o u r s , th e a v e ra g e b e in g 20 h o u rs 33 I n 2 i n s t a n c e s th e r a t s were k i l l e d a f t e r b la d d e r e x p e rim e n t a t i o n , and th e s e would have no doubt l i v e d s e v e r a l h o u rs lo n g e r . I n none o f th e r a t s d e c e r e b r a t e d u s in g t h i s te c h n iq u e d id th e an im a l d i e im m e d ia te ly a f t e r d e c e r e b r a t i o n . I n o n ly 1 i n s t a 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 te d . The s u r v i v a l p e r io 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 te ly lo n g f o r th e d u r a t i o n o f th e e x p e rim e n t i n a l l 6 c a s e s . The s u p e r i o r i t y of t h i s method a s compared to p re v io u s ones i s p ro b a b ly e x p la in e d by s e v e r a l f a c t o r s . I n f i l t r a t i o n w ith a l o c a l a n e s t h e t i c a llo w s a s u f f i c i e n t l y low dosage of g e n e r a l a n e s t h e s i a to p r e v e n t mucus f o r m a tio n i n th e r e s p i r a t o r y t r a c t , and y e t p e rm its a s u f f i c i e n t d e g re e o f l o c a l d e s e n s i t i z a t i o n which a l l e v i a t e s sh o ck . Ad m i n i s t r a t i o n o f ca lc iu m g lu c o n a te p ro v id e s a means o f m in im iz in g hem orrhage s u b se q u e n t to rem oval o f th e s k u l l , th u s p r e v e n t i n g sh o ck . 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 rem oval o f t i s s u e a llo w in g a c l e a r l y v i s i b l e f i e l d and a c c u r a t e d e t e r m in a ti o n o f th e r e g io n o f t r a n s e c t i o n . The whole p ro c e d u re was sim p le and d i r e c t , r e q u i r i n g l i t t l e a p p a r a t u s , and l i t t l e tim e f o r th e com plete o p e r a t i o n . R ec o rd in g a p p a r a t u s . ’ //hen th e e x p e rim e n ts were f i r s t begun, a s e t - u p s i m i l a r to t h a t d e s c r i b e d by D*Amour and Blood (1 9 4 8 ), was u se d i n an a tte m p t to r e c o r d i n t r a v e s i c a l p r e s s u r e s . I n t h i s p r o c e d u re , a s i n g l e c a n n u la a t t a c h e d to one arm of a T -tu b e was i n s e r t e d i n t o th e b l a d d e r . F l u i d was 34 i n tr o d u c e d from a s y r i n g e c o n n e c te d to th e second arm o f the T - tu h e . The re m a in in g arm was a t t a c h e d to th e r e c o r d in g tam b o u r . This arra n g e m e n t was found to be e n t i r e l y in a d e q u a te f o r s e v e r a l r e a s o n s : 1 ) . upon i n j e c t i o n o f p e r f u s a t e , t h e r e was no i n d i c a t i o n o f th e amount which a c t u a l l y e n te r e d th e b l a d d e r ; S ) . h a v in g no tu b e i n t e r p o s e d betw een th e r e c o r d i n g tambour and th e s y r i n g e , f l u i d 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 to keep th e c o n n e c tin g tu b in g f r e e of a i r b u b b le s . The a p p a r a tu s f i n a l l y assem b led f o r e x p e r im e n ta l work was a g r e a t l y m o d ifie d v e r s i o n o f th e above and th e arra n g e m e n t i s d ia g r a m m a tic a lly r e p r e s e n t e d i n F ig u re 1 . No a tte m p t was made to draw th e components i n p r o p o r t i o n a t e s i z e s in c e d e t a i l o f s m a ll p a r t s was em p h asiz ed . The draw ing r e p r e s e n t e d h e r e i n c l u d e s th e w a te r manometer u se d i n c a l i b r a t i n g th e system i n term s o f cm. w a te r p r e s s u r e . D uring 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 , how ever, the c a n n u la was i n s e r t e d i n t o th e u r i n a r y b la d d e r and th e manometer was e l i m i n a t e d from th e s e t - u p . P h o to g rap h s o f th e a p p a r a tu s u sed 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 a r e shov/n i n F ig u re s 2 and 3 . Two c o n c e n t r i c c a n n u la e were c o n s t r u c t e d from 2 hypo derm ic n e e d l e s , 16 and 22 gauge. The 16 gauge n e e d l e , th e one o f l a r g e r d ia m e te r , was c u t a b o u t 4 ram, d i s t a l to th e h u b . The c u t p o r t i o n i n c l u d i n g th e hub o f th e n e e d l e , was th e n i n s e r t e d a t r i g h t a n g le s t o , and mid-way betw een th e ends of th e r e - 35 m a in in g p o r t i o n o f th e n e e d l e , so t h a t a T -tu b e c o n f i g u r a t i o n r e s u l t e d . The 22 gauge n e e d le was i n s e r t e d i n s i d e th e c ro s s p i e c e o f th e T -tu b e a rra n g e m e n t ( througti th e lo n g a x i s ) and th e j o i n t s were s o ld e r e d a i r - t i g h t . The p e r f u s a t e from th e s y r in g e was d e l i v e r e d 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 t h i s system c o u ld be opened or c lo s e d by means of 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 la . The o u ts id e c a n n u la a c te d as a j a c k e t e n c l o s in g th e s m a l l e r c a n n u la , and form ed a cham ber, a l l tim es c o n tin u o u s w ith th e v e r t i c a l tube and i n t u r n , th e r e c o r d i n g tam bour. Thus, th e u se of such a d o u b le c o n c e n t r i c c a n n u la e e n a b le d s im u lta n e o u s i n t r o d u c i n g of f l u i d i n t o th e b l a d d e r , and r e c o r d in g o f r e a c t i o n a r y v e s i c a l a c t i v i t y ; such an arran g e m e n t a l s o e l i m i n a t e d th e n e c e s s i t y of e x c e s s i v e , cumbersome t u b in g . A v o l u m e - c a l ib r a t e d v e r t i c a l tu b e , i n s e r t e d i n t o th e hub o f th e o u t s i d e c o n c e n t r i c ca n n u la was in tr o d u c e d i n th 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 th e volume of p e r f u s a t e e n t e r i n g th e b la d d e r on i n j e c t i o n of f l u i d , s in c e a c e r t a i n amount of f l u i d i n j e c t e d was fo rc e d i n t o th e v e r t i c a l tube by th 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 . Knowing th e volume o f p e r f u s a t e i n j e c t e d from th e s y r i n g e , and knowing th e volume o f f l u i d which r o s e i n th e v e r t i c a l tu b e , th e volume i n tr o d u c e d i n t o th e b la d d e r c o u ld be d e te rm in e d . The a p p a r a tu s was so c o n s t r u c t e d , t h a t c o n n e c tio n to and d is c o n n e c t io n from th e c a n n u la e , th e s y rin g e and th e 36 Screw clamp R ec o rd in g tambour Kymograph .V e rtic a l tube ( c a l i b r a t e d i n .25 c c . ) -Water manometer Removable f i t t i n g s Rubber n i p p l e ,Two-way s to p - c o c k C o n c e n tric can n u la e S y rin g e FIGURE 1 RECORDING APPARATUS SET-UP FOR CALIBRATION il 37 R ec o rd in g tambour V e r t i c a l tu b e W ater manometer .C o n c e n t r ic c an n u lae FIGURE 2 THE APPARATUS AS SET UP FOR RECORDING INTRAVESICAL PRESSURES IN THE RAT 38 V e r t i c a l tu b e Water manometer M o ist chamber C o n c e n tric can n u la e FIGURE 3 PHOTOGRAPH SHOWING THE CONCENTRIC CANNULAE INSERTED INTO THE URINARY BLADDER 39 v e r t i c a l column was sim p le and q u ic k . At f i r s t le a k a g e a t th e s e j u n c t i o n s o c c u r re d when p r e s s u r e i n th e system ro se f a i r l y h i g h . However, i t was l a t e r found t h a t a p p l i c a t i o n of a s m a ll amount o f s to p - c o c k g r e a s e around th e f i t t i n g s was a sim p le and q u ic k means of a s s u r i n g a le a k p r o o f sy stem . The v e r t i c a l column was e a s i l y f lu s h e d by means of opening th e clamped ru b b e r tu b in 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 tu s u se d by B a r r in g to n (1 9 1 4 ), i n h i s s t u d i e s i n c a t s , and i n th e r e c o r d in g a p p a r a tu s u se d by Lew is, Langw orthy, and Dees (1935), i n e x p e rim e n ts p e r formed on human s u b j e c t s , a c a t h e t e r was p a sse d th ro u g h th e u r e t h r a i n t o th e b la d d e r and th e b la d d e r was d is te n d e d w ith f l u i d 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 th e r e s e r v o i r and th e c a t h e t e r was used as a w a te r m anom eter. No a c c o u n t was made o f th e volume o f f l u i d i n th e v e r t i c a l tu b e i n o r d e r to d e te rm in e th e a c t u a l volume o f th e b la d d e r c o n t e n t s . P erhaps i n l a r g e r a n im a ls , t h i s amount 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 th e r a t i n which in c re m e n ts were o n ly .2 c c . , i t would seem im p o rta n t to a c c o u n t f o r volume i n th e v e r t i c a l column. I t i s n o te d t h a t i n th e methods d e s c r ib e d by B a r r in g to n (1 9 1 4 ), and by Lewis e t a l (1 9 3 5 ), th e i n t r a v e s i c a l p r e s s u r e s were re a d d i r e c t l y from th e v e r t i c a l column. I n th e p r e s e n t i n v e s t i g a t i o n , how ever, th e system was c a l i b r a t e d i n term s o f w a te r p r e s s u r e u s in g th e s e t - u p shown i n F ig u re 1. W ater 40 was in tr o d u c e d i n t o th e w a te r manometer from th e s y r i n g e , by way of th e c a n n u la e jo in e d by a r u b b e r n i p p l e to th e h o r i z o n t a l arm o f th e m anom eter. At 5 cm. w a te r p r e s s u r e i n t e r v a l s , as i n d i c a t e d by th e manometer r e a d i n g s , th e c o r re s p o n d in g r i s e o f t h e . w r i t i n g arm o f th e tam bour was re c o rd e d k y m o g ra p h ic a lly • The c a l i b r a t i o n cu rv e v/as p l o t t e d , th e o r d in a te r e p r e s e n t i n g r i s e i n mm. o f th e w r i t i n g arm, th e a b s c i s s a r e p r e s e n t i n g cm. w a te r 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 c u rv e i s shovm i n F ig u re 4 . The kymogram r e c o r d s o b ta in 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 easured and th e h e i g h t s i n mm. o f th e r e c o rd in g s were i n t e r p r e t e d i n term s of cm. w a te r p r e s s u r e u s in g th e c a l i b r a t i o n c u r v e . With t h i s a rra n g e m e n t, a g iv e n p r e s s u r e i n th e w a te r manometer r e p r e s e n t e d the a c t u a l b l a 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 of th e v e r t i c a l column. A r e a d in g i n th e w a te r manom eter, f o r example 5 cm. w a te r p r e s s u r e , r e p r e s e n t e d a p p ro x im a te ly 25-30 cm. w a te r i n th e v e r t i c a l colum n, th u s 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 ec o rd in g p r o c e d u r e . A f t e r d e c e r e b r a t i n g th e a n im a l, a minimum o f 1 h o u r was allo w ed f o r r e c o v e r y from a n e s t h e s i a b e f o r e p e r f u s i n g th e b la d d e r and r e c o r d i n g th e r e a c t i o n a r y b l a d d e r a c t i v i t y . 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 an im a l b o a rd , and th ro u g h a lov; v e n t r a l abdom inal m i d - l i n e i n c i s i o n , a p p ro x im a te ly 2 cm. i n l e n g t h , th e u r i n a r y b l a d d e r was e x p o sed . A s m a ll s n ip was made i n th e b la d d e r w a l l , on th e d o r s a l s id e n e a r th e ap ex . The c o n c e n t r i c cL H -rn ilixTi: 3^S±t: i i _ : -lLÜ ai-irblrit “ h - j 4 -("rtrrr lîlE H Ît -U _ U - , L 1 ^|..LUJ - rH L bzd-rm i j± 4 p 0 B . L Ü ± h Ü i 16 I i Z - o No. 62Û1-T, U niversity Bookstore, Los Angeles 42 c a n n u la e were i n s e r t e d and u s in g a s m a ll cu rv ed c u t t i n g - n e e d l e , s e v e r a l s m a ll s t i t c h e s were p a sse d around the b la d d e r i n c i s i o n and th e th re a d ends were t i e d around th e c a n n u la e . With th e c an n u lae i n p l a c e , 1 s i n g l e th re a d was th en t i e d around th e b la d d e r i n c i s i o n , to th e c a n n u la e , w ith c a re to i n c lu d e j u s t enough o f th e b la d d e r t i s s u e to a s s u r e a c o m p le te ly l e a k - p r o o f system . The s y r in g e and th e t i p o f th e v e r t i c a l tu b e were i n s e r t e d i n t o 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 in u te i n t e r v a l s , 0 .2 c c . p e r f u s a t e was slo w ly i n j e c t e d i n t o th e b l a d d e r . The s to p - c o c k b e in g c lo s e d im m e d ia te ly a f t e r i n j e c t i o n , b la d d e r p r e s s u r e s were r e c o rd e d by means of th e w r i t i n g tambour on a kymograph drum r e v o lv in g a t th e r a t e of 8 mm./ se c o n d . The volume i n th e v e r t i c a l column was re a d 1 m in u te a f t e r i n j e c t i o n o f f l u i d i n t o th e b la d d e r i n th e f i r s t s e r i e s o f e x p e rim e n ts , and i n th e re m a in in g e x p e r im e n ts , r e a d in 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 ll as 1 m in u te 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 were k e p t m o iste 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 in g th e a r e a . This o f c o u rse o b scu red th e b la d d e r so t h a t o b s e r v a t i o n of i t s s t a t e 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 im p o s s ib le . L a t e r , a sm a ll m o ist-c h a m b e r (made by c u t t i n g th e ro u n d ed -en d o f a t r a n s p a r e n t p l a s t i c t e s t - t u b e ) was u se d which was e f f e c t i v e i n p r e v e n t i n g d r y in g o u t of th e b la d d e r t i s s u e , and s t i l l p e r m it t e d o b s e r v a t i o n o f b la d d e r a c t i v i t y . 43 I n th e f i r s t s e r i e s of e x p e rim e n ts, u s in g 4 r a t s , (T ab les III-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 th e b la d d e r f o r com parison of b l a d d e r a c t i v i t y : i s o t o n i c s a l i n e 0 . 8 5 / , pH 5 .2 ; S o ren sen ^s b u f f e r m ix tu r e s , pH 1 .0 5 and pH 3 .3 2 . I n th e second s e r i e s of e x p e rim e n ts , u s in g 5 r a t s , (T ab les XVII-XXVII), i s o t o n i c s a l i n e , 0 . 8 5 / , pH 5 . 2 , and ri S o ren sen ^ s b u f f e r m ix tu r e s , pH 4 .5 2 , pH 8 .4 , and pH 9 .1 were u sed i n a co m p a ra tiv e s tu d y of b la d d e r a c t i v i t y . I n th e p re v io u s e x p e rim e n ts , th e b la d d e r was p e r f u s e d w ith s a l i n e , is o s m o tic w ith th e serum; th e 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 sm o tic o r hypoosm otic 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 in 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 due p r i m a r i l y to d i f f e r e n c e s i n pH o r to d i f f e r e n c e s i n osm otic p r e s s u r e s of th e s o l u t i o n s , th e l a s t e x p e rim e n t, u s in g 1 r a t (T a b le s XXVIII-XXX), was ru n to compare th e e f f e c t s of p e r f u s i o n w ith b u f f e r s o l u t i o n , pH 6 .8 8 and is o s m o la r s a l i n e , pH 5 .1 ; b u f f e r s o l u t i o n , pH 9 .1 and is o s m o la r s a l i n e , pH 5 .3 ; b u f f e r s o l u t i o n , pH 2 .1 8 and is o s m o la r s a l i n e , pH 5 . 1 . A Beckman pH m e te r was u sed to d e te rm in e th e pH o f th e s a l i n e s o l u t i o n s . The b u f f e r s o l u t i o n s were p r e p a re d from th e f o llo w in g m a t e r i a l s in th e amounts shov/n i n Table 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 tly 0 .1 N HGl s o l u t i o n c) E x a c tly 0 .1 N NaOH s o l u t i o n 44 TABLE II 1 1 SORENSEN'S BUFFER MIXTURES pH G lycine/N aC l NaOH HGl R a tio Is o s m o la r c o n c . m ix tu re c c . c c . osm olar co n c. NaGl gm ./400 c c . CO. b u f f e r a n d i s o t o n i c s a l i n e b u f f e r / s a l i n e 2 .1 8 240 160 0 .9 0 6 3 .0 8 5.88 400 1 .0 4 3 .5 3 6 9 .1 320 80 ____ 0 .9 6 3 .264 1 .0 5 40 360 0 .3 7 3 .3 2 360 40 0 .6 6 4 .5 2 396 4 0 .6 8 8 .4 380 20 0 .6 7 45 The r a t i o o f th e osm olar c o n c e n t r a t i o n o f th e 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 s a l i n e s o l u t i o n i s i n d i c a t e d i n th e t a b l e . The is o s m o la r c o n c e n t r a t i o n o f NaGl i n g ./4 0 0 c c . i s i n d i c a t e d f o r th e s o l u t i o n s i n th e t h i r d e x p e rim e n t. The c o n c e n t r a t i o n o f NaGl i n g ./4 0 0 c c . , is o s m o tic w ith th e b u f f e r m ix tu re was d e te rm in e d by c a l c u l a t i n g th e number o f m oles of 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 p r e s e n t i n 400 c c . b u f f e r s o l u t i o n . A sample c a l c u l a t i o n , f o r b u f f e r s o l u t i o n pH 2 .1 8 , was as f o llo w s : 1. Grams o f Each G o n s tit u e n t / 400 c c . S o l u t i o n = (c c . x grams) 1000 G ly cin e 240 x 7 .5 0 5 g. - 1.801 g ./2 4 0 c c . 100Ô NaGl 240 x 5 .8 5 g. = 1.404 g ./2 4 0 c c . 1000 HGl 160 X 3 .6 4 6 g. = 0.5 8 4 g . / l 6 0 c c . 1000 2. Osmolar G o n c e n tra tio n = grams x number o s m o t i c a l l y M o le c u la r w t. a c t i v e p a r t i c l e s produced by 1 m o lecu le B u ffe r M ix tu re : G lycine 1 .8 0 1 = 0 .0239 x 1 = 0.0239 7 5 .0 5 NaGl 1 .4 0 4 = 0.0 2 4 1 x 2 = 0.0482 58.45 HGl 0 .5 8 4 = 0 .0 1 6 x 2 = 0 ,032 3-67477 0.1041 T o t a l number o f m oles o f s o m o t i c a l l y a c t i v e p a r t i c l e s / 4 0 0 cc. 46 I s o t o n i e S a l i n e : 8 .5 g . / l . = .1 4 3 6 X 400 x 2 = 0 .1 1 4 8 8 ■55745 lÜSÜ 3 . S a l i n e Is o s m o tic With B u f f e r S o l u t i o n = osm olar c o n c . buf f e r x ( g. NaGl / 400 o c .) osm olar co n c. s a l i n e 0 .1 0 4 1 : 0 .906 X 3 .4 g ./4 0 0 o c. = 3 .0 8 g ./4 0 0 c o . 5 7 1 1 3 5 8 47 P r e s e n t a t i o n o f e x p e r im e n ta l d a t a . D ata from th e s e r i e s of e x p e rim e n ts u s in g 8 r a t s a p p e a r i n th e f o llo w in g t a b l e s and g r a p h s . I n 7 r a t s , s e v e r a l t r i a l s were ru n and b la d d e r p r e s s u r e s were r e c o rd e d u s in g th e same r a t i n o r d e r to compare th e r e a c t i o n s o f a s i n g l e b la d d e r to v a r io u s p e r f u s a t e s . Data from each t r i a l a p p e a r i n t a b l e s i n th e o r d e r i n which th e t r i a l s were r u n . The kyraograms o b ta in e d d u r in g each p e r f u s i o n o f th e b la d d e r were m easu red , 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 te r , u s in g th 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 re c o rd i s shown i n F ig u re 5. From each r e c o r d , th e i n i t i a l p r e s s u r e i n cm. w a te r r e s u l t i n g upon c o m p le tio n of each i n j e c t i o n of p e r f u s a t e , and th e f i n a l p r e s s u r e , r e s u l t i n g a t th e end o f 2 m in u te s (im m e d ia te ly p r e c e d in g th e f o llo w in g i n j e c t i o n ) , were d e te rm in e d and com piled i n th e r e s p e c t i v e t a b l e s . 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 , th e s e v a lu e s were th e n p l o t t e d g r a p h i c a l l y , th e o r d 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 term s o f cm. w a te r , th e a b s c i s s a r e p r e s e n t i n g volume of p e r f u s a t e i n tr o d u c e d i n t o th e sy ste 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 as i l l u s t r a t e d i n th e f o llo w in g d ia g ra m . 4 - , ;ri, 4 t4 I t l*fa z-o C.C, ■ ( r y e c-ieJ 48 Where a drop i n p r e s s u r e i s shown, w ith no i n d i c a t i o n o f lo s s o f f l u i d from th e b la d d e r th ro u g h th e u r e t h r a , a d a p t a t i o n o f th e b la d d e r o c c u r re d . 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 , 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 , th e volume o f f l u i d e li m i n a t e d t h r o u ^ th e u r e t h r a was d e te rm in e d and in c lu d e d i n th e t a b l e s . However, i n some i n s t a n c e s when th e h ig h fre q u e n c y o f d r i b b l i n g and th e h y p e r a c t i v i t y o f th e an im al 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 re ly i n d i c a t e d t h a t l o s s o f f l u i d had o c c u r r e d . Two term s h av e been u sed to i n d i c a t e l o s s of f l u i d th ro u g h th e u r e t h r a ; " d rib b le " a n d r e f l e x m i c t u r i t i o n . R e f le x m i c t u r i t i o n was u s e d to i n d i c a t e em ptying o f th e b la 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 io d i n which th e b l a d d e r p r e s s u r e dropped a t th e c o m p le tio n of th e a c t to a low a p p ro x im a tin g th e i n i t i a l p r e s s u r e . W hereas, i n o t h e r c a s e s , where f r e q u e n t l o s s of f l u i d o c c u rre d from th e u r e t h r a i n amounts of 1 o r 2 d r o p s , d u r a t i o n b e in g v e ry s h o r t , and where no a p p a r e n t f o r c e f u l s tre a m in g o f f l u i d from th e u r e t h r a o c c u r re 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 ta in e d from a l l th e e x p e r im e n ta l r a t s were a n a ly z e d and c o n s o li d a t e d and a p p e a r i n Table XXXI, page 93. 49 FIGURE 5 PHOTOGRAPH OF AN ORIGINAL KYÎvlOGRAM SHOWING REACTIONARY VESICAL ACTIVITY IN RESPONSE TO VARIOUS PERFUSATES IN DECEREBRATE RAT #8 TABLE III RAT #1--DEGEREBRATE, ANALYSIS OF KYMOGRAM SHOWING RESULTANT VESICAL PRESSURES USING SALINE PERFUSATE 50 F lu id Volume i n F lu id r e l e a s e d i n j e c t e d v e r t i c a l tube from b la d d e r H t. i n mm. re c o rd e d P r e s s u re cm. w a te r c c . c c . th ro u g h u r e t h r a i n i t i a l f i n a l i n i t i a l f i n a l 0 .2 •ir # 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 1 1.0 1 .8 8 .6 7 .5 14.0 12.0 2 .0 12.0 1 0 .0 2 2 .0 17.0 2 .2 12.6 1 1 .0 1 8 .5 19 .5 2 .3 R e fle x m i c t u r i t i o n 12.2 2 .0 2 2 .5 2 .5 ir I n t h i s f i r s t e x p e rim e n t, no r e c o rd was k e p t of th e volume in 1 th e v e r t i c a l volumn. No lo s s o f f l u i d from th e u r e t h r a o c c u rre d u n t i l 2 .3 c c . had been i n j e c t e d when r e f l e x m i c t u r i t i o n to o k p l a c e . %|rn:q:ii rqg;: |:i_ r |4:±' — rrrr' Hy T'TT i1 i 'iT n^n+ l r:d±ttrbxti: T - f ^ rR -n-qp ± i-X i: r±n tti n ^ a i x E t L ! ; i i - f — j ~ — - I'll I I rri-H-i i ri'~|-r!~ i~ i " im îrNitfertEl: m itë ë f f iîR S f f lï # s a i t ■ ;'Tljt-H h! i=:|:Xjteb L h trrrr.i ! — X } - • 1 II n pSrRtl'ÈB n-rai h:fd:;xq irPiR FPC fR fR H /rTTirrr ' f'n v 'X d '" I 'l" ''’ } i T — T , - T " ! - r - T - i “7 RptfRrp I'i |!|i I |_x|l|^jyH ±rbqtH :|'R| :q;tm -;xriyprq{:i:jxnitX f , jT lT -p ttp i 5 T t% :l:!:|_ jji ! 'mil Tnin-'l' " T M 'iT r /m R i ËR tÎ ! j:H -;'i;t I -l-R t ittt±ïb±Ed-xb-; t z E t m m s U xijj [:n|; itiE-ptq q'tR-'bd.RiJXLrd 1— j_.l_L.l_l_, i l'ri'H iriîlx L l 1 -i-r »-i-;-'-i r '|= u 7 ':- hr ' r " I î:ixd;xt|:jd|! ' ' ' iiy+iii lU ;i± T 2 -1 ' = H '* f rr'iT ^ 'rT rr Id ' ' i i ' -x -fr-T — '- H N R i + d R H 4 H i ' i d i d d l r " " : | iT: I d ' . Î :R-rrr:N:dd-":x::diddX!d...... 1 " i + !JJ4i-iT !'rfr tLtSJiiaSEiri-'ltnii " o • ^ 0 \i I'I I 1 ! J i ! i . a - V ;* f N o. 6 2 0 ] T, UMiVEPSi'i Y BoorüTüH y. L os Aur TABLE IV RAT #2--DECEREBRATE, ANALYSIS OP KYMOGRAM SHOmNG RESULTANT VESICAL PRESSURES USING SALINE PERFUSATE 52 F lu id i n j e c t e d cc • Volume i n v e r t i c a l tu b e c c . F l u i d r e l e a s e d from b la d d e r th ro u g h u r e t h r a c c . H t. i n mm. r e c o rd e d i n i t i a l f i n a l P r e s s u r e cm. w a te r i n i t i a l f i n a l 0 .2 — 0 1 .5 1 .5 1 .5 1 .5 0 .4 0 .1 2 0 3 .0 3 .0 4 .0 4 .0 O.G 0 .2 4 0 5.0 5 .0 7 .5 7 .5 0 .8 0 .4 0 0 .2 7 .0 7 .0 1 1.0 11.0 1 .0 0 .5 2 0 8 .0 8 .0 12 .6 12.6 1 .2 0 .5 8 0 9 .5 8 .0 16.0 12.6 1 .4 0 .5 8 0 .2 9 .6 8 .5 16.2 13 .5 1 .6 0 .4 2 0 10 .0 1 0 .0 17 .0 17.0 1 .8 0 .6 5 0 .3 1 1.6 9 .0 2 1 .0 1 5 .0 2 .0 0 .6 3 0 1 0 .0 9 .0 17 .0 1 5 .0 2 .2 0 .5 2 0 1 1.0 1 1 .0 19.5 1 9 .5 2 .4 0 .5 2 0 .3 1 2 .0 8 .9 2 2 .0 1 4 .5 2 .6 0 .6 3 0 .2 1 0 .0 9 .0 17.0 15.0 2 .8 0 .7 7 ?v- 11.0 10.0 19.5 17.0 3 .0 0 .4 8 0 .5 1 2.0 9 .5 2 2 .0 16.0 3 .2 0 .6 5 ? .;C - 11.0 9 .0 1 9 .5 15.0 3 .4 0 .5 0 0 .3 10.0 5 .5 1 7.0 8 .0 Loss of f l u i d th ro u g h u r e t h r a ; volume e l i m in a te d unknown. TABLE V 55 RAT #2--DECEREBRATE, ANALYSIS OP KYMOGRAM SHOWING RESULTANT VESICAL PRESSURES USING SALINE PERFUSATE P lu id i n j e c t e d c c . Volume i n v e r t i c a l tubo c c . P lu id r e l e a s e d from b la d d e r th ro u g h u r e t h r a c c . H t. i n mm. re c o rd e d i n i t i a l f i n a l P r e s s u r e cm. w a te r i n i t i a l f i n 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 1 5 .0 1 5.0 0 .8 0 .8 3 0 10.5 1 0 .5 1 8 .0 18.0 1 .0 1 .0 5 0 13.0 1 2 .6 2 5 .0 2 1 .8 1 .2 1 .2 0 15.0 1 4 .1 3 0 .0 2 7 .5 1 .4 1 .2 0 16.0 1 4 .0 3 3 .0 2 7 .5 1 .6 1 .0 3 13.0 12.0 2 5 .0 2 2 .0 1 .8 0 .8 5 0 .2 14.0 1 0 .0 2 7 .5 1 7.0 2 .0 0 .8 3 0 13 .0 10.0 2 5 .0 1 7 .0 2 .2 0 .9 8 0 1 2 .0 1 2 .0 2 2 .0 2 2 .0 2 .4 0 .9 0 0 .2 13 .0 1 1 .0 2 5 .0 1 9 .5 2 .6 0 .9 1 0 .4 12 .0 9 .5 2 2 .0 16.0 2 .8 0 .9 3 0 12 .0 11.8 2 2 .0 2 1 .6 3 .0 0 .9 5 0 13.5 11 .5 2 6 .5 2 1 .0 3 .2 0 .7 0 .4 13.0 9 .0 2 5 .0 15.0 3 .4 0 .5 0 10.0 6 .5 1 7.0 9 .8 3 .6 0 .6 5 0 9 .3 8 . 5 15 .5 13.5 3 .8 0 .8 0 0 10.0 9 .0 17.0 15.0 4 .0 0 .7 8 0 .4 12.0 8 .0 2 2 .0 12. J Loss o f f l u i d th ro u g h u r e t h r a ; volume e lim in a te d unknown. I u - a .Y O ' V /. I, N o . 6 2 0 1 T , U n i v e r s i t y B a a K S T O R E , L o s a n o e u e s TABLE VI RAT #2— DECEREBRATE, ANALYSIS OP KYÎ/ÎOGRAM SHOWING RESULTANT VESICAL PRESSURES USING PERFUSATE, pH 1.05 55 F lu id i n j e c t e d c c . Volume i n v e r t i c a l tu b e c c . F lu id r e l e a s e d from b la d d e r th ro u g h u r e t h r a H t. i n mm. r e c o rd e d i n i t i a l f i n a l P r e s s u r e cm. w a te r i n i t i a l f i n a l 0 .2 0 3 .5 3 .0 5 .0 4 .0 0 .4 0 .3 6 0 6 .0 4 .7 9 .0 7 .0 0 .6 0 .4 5 0 7 .0 5 .0 11.0 7 .5 0 .8 0 .2 4 0 6 .0 2 .0 9 .0 2 .5 1 .0 0 .2 4 0 5 .0 3 .5 7 .5 5 .0 1 .2 0 .2 4 0 5 .5 3 .3 8 .0 4 .8 1 .4 0 .3 2 0 5 .0 4 .7 7 .5 7 .0 1 .6 0 .5 5 0 7 .6 7 .6 12 .0 1 2 .0 1 .8 0 .7 3 0 10 .0 1 0 .0 17.0 1 7 .0 2 .0 0 .5 3 0 1 3 .0 4 .8 2 5 .0 7.0-:h;- 2 .2 0 .5 0 0 7 .2 7 .0 11.0 1 0 .0 2 .4 0 .4 5 0 8 .3 6 .3 1 3 .5 9 .5 2 .6 0 .2 4 0 8 .0 3 .0 12.5 4 .0 2 .8 0 .3 2 0 5 .0 5 .0 7 .5 7 .5 3 .0 0 .2 4 0 6 .5 1 .0 10.0 0 .5 3 .2 0 .2 4 0 3 .5 2 .0 5 .0 2 .5 S l i g h t le a k a g e o c c u rre d a t th e j u n c t i o n o f th e v e r t i c a l tube and th e c a n n u la . TABLE VII 56 RAT #2--DEGSREBRÂTS, ANALYSIS OP KYÎÆOGRAM SHOWING RESULTANT VESICAL PRESSURES USING SALINE PERFUSATE F lu id i n j e c t e d c c . Volume in v e r t i c a l tube c c . P lu id r e l e a s e d from b l a d d e r th ro u g h u r e t h r a c c . H t. i n mm. r e c o rd e d i n i t i a l f i n a l P r e s s u re cm. w a te r i n i t i a l f i n a l 0 .2 0 2 .5 2 .5 3 .0 3 .0 0 .4 0 4 .0 4 .0 6 .0 6 .0 0 .6 0 .4 2 0 5 .5 5 .5 8 .0 8 .0 0 .8 0 .5 5 0 7 .2 7 .2 11.3 11.3 1 .0 0 .7 0 0 9 .5 9 .0 1 6 .0 15.0 1 .2 0 .6 7 0 10.5 9 .0 18.0 1 5 .0 1 .4 0 .7 3 0 10.0 9 .5 17.0 16.0 1 .6 0 .7 3 ?* 1 1 .0 9 .0 1 9 .5 15.0 1 .8 0 .8 0 0 1 1.0 10.5 1 9 .5 18.0 2 .0 0 .4 5 0 .4 11.5 9 .0 2 1 .0 15 .0 2 .2 0 .5 8 0 11.0 1 0 .5 1 9 .5 18.0 2 .4 0 .7 0 0 1 2 .0 8 .0 2 2 .0 12.5 2 .6 0 .6 5 0 .4 1 0.0 7 .5 1 7 .0 12.0 2 .8 0 .7 2 0 10.0 1 0 .0 1 7 .0 1 7 .0 3 .0 0 .8 3 0 12.0 11.0 2 2 .0 1 9.5 3 .2 0 .9 0 0 12.0 1 1 .5 2 2 .0 2 1 .0 3 .4 0 .8 3 0 .2 14.0 1 0 .0 2 7 .5 17 .0 3 .6 0 .8 3 19.0 8 .0 2 7 .5 12.5 3 .8 0 .7 0 0 9 .0 9 .0 15.0 1 5 .0 4 .0 0 .8 5 0 11.0 11.0 1 9.5 1 9 .5 4 .2 1.03 0 14 .0 1 1.0 2 7 .5 1 9.5 - Î 5 - Loss o f f l u i d th ro u g h u r e t h r a ; voliame e lim i n a t e d unknov/n. s a p S u v soq ‘3jop'>[00[j .C^isjaAtiri '±-iQZ9 "K M i V is I % TABLE VIII 58 RAT #3— I^ÏEMBUTAL ANESTHESIA. ANALYSIS OP KYMOGRAM SHOWING RESULTANT VESICAL PRESSURES USING SALINE PERFUSATE F lu id i n j e c t e d cc • Volume i n v e r t i c a l tube c c . F l u i d r e l e a s e d from b la d d e r th ro u g h u r e t h r a c c . H t. i n mm. re c o rd e d i n i t i a l f i n a l P r e s s u r e cm. w a te r i n i t i a l f i n a l 0 .2 0 1 .3 1 .3 1 .0 1 .0 0 .4 0 .2 8 0 4 .0 4 .0 6 .0 6 .0 O.G 0 .4 8 0 5 .6 5 .6 8 .3 8 .3 0 .8 0 .6 5 0 6.8 6 .0 10.5 9 .0 1.0 0 .6 0 0 7 .9 7 .0 12.5 11.0 1 .2 0 .7 0 0 9 .2 8 .0 15.3 12 .5 1 .4 0 .7 0 11 .0 8 .0 1 9.5 12 .5 1.6 0 .7 8 0 10.0 8 .0 17.0 12.5 1 .8 0 .6 8 ?'« * 11 .2 8 .0 2 0 .1 12 .5 2 .0 0 .6 5 0 .4 11.2 7 .9 2 0 .1 12 .5 2 .2 0 .7 0 0 10.3 8 .2 17.6 1 3 .0 2 .4 0 .6 5 0 1 1 .0 8 .0 1 9 .5 1 2 .5 2 .6 0 .3 8 .5 4 .0 1 3 .5 6 • O " )!" ^ '- 2 .8 0 .5 4 0 7 .0 6.0 11.0 9 .0 3 .0 0 9 .0 6 .0 15.0 9 .0 * * * Loss of f l u i d th ro u g h u r e t h r a ; volume e lim i n a t e d unknov/n, -;h:- Leakage o c c u rre d a t th e v e r t i c a l tube c a n n u la j u n c t i o n . TABLE IX RAT #3--NEMBUTAL ANESTHESIA, ANALYSIS OP KYMOGRAM SHOWING RESULTANT VESICAL PRESSURES USING PERFUSATE, pH 3.3 59 F lu id i n j e c t e d c c . Volume i n v e r t i c a l tube c c . F lu id r e l e a s e d from b la d d e r th ro u g h u r e t h r a CO . H t. i n mm. r e c o rd e d i n i t i a l f i n a l P r e s s u r e cm. w a te r i n i t i a l f i n a l 0 .2 0 2 .7 2 .7 3 .5 3 .5 0 .4 0 .2 0 0 5 .0 4 .2 7 .5 6 .0 0 .6 0 .4 8 0 6 .2 6.0 9 .3 9 .0 0 .8 0 .7 8 0 9 .0 7 .0 15.0 11.0 1 .0 0 .6 0 0 10.0 7 .0 17.0 1 1 .0 1.2 0 .7 3 0 10.0 8 .3 17.0 13.5** 1 .4 0 .7 0 ?* 12.1 5 .5 2 2 .5 8 .0 1 .6 0 .6 5 0 8 .7 7 .7 1 4 .0 12.0*** 1.8 0 .7 0 0 9 .0 7.0 15 .0 11.0 2 .0 0 .7 8 0 10.0 9.0 17.0 1 5 .0 2 .2 0 .9 0 0 .4 11.6 6.0 2 1 .0 9 .0 2 .4 0 .5 0 0 6 .3 6.3 9 .5 9 .0 2 .6 0.5 8 0 7 .2 6 .9 11.0 10.5 2 .8 0 .6 0 0 8 .2 6 .9 13 .0 1 0 .5 3 .0 0.5 8 0 8 .2 7 .0 1 3 .0 11.0 3 .2 0 .6 0 0 8 .5 7 .0 1 3 .5 11.0 3 .4 0 .6 0 0 8 .2 7 .0 1 3 .0 11.0 3 .6 0 .6 3 0 8 .2 7 .0 13.0 11.0 3 .8 0 .6 0 0 8 .0 7 .0 1 2 .5 1 1 .0 4 .0 0 .6 0 0 8 .2 3 .0 1 3.0 4 .0 * Loss o f f l u i d th ro u g h u r e t h r a ; volume e lim i n a t e d unknown ** Animal u n d e r v e ry 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 . nem butal i 3 L 6 .1 C X ÿ t. te . No. 6201-T, Univeisit}- Bookstore, Los Angeles 1.0 3.2. TABLE X 61 RAT #3--DSGEREBRATE, ANALYSIS OP KYMOGRAM SHOWING RESULTANT VESICAL PRESSURES USING SALINE PERFUSATE P lu id Volume i n P lu id r e l e a s e d H t. i n mm. i n j e c t e d v e r t i c a l tube from b la d d e r re c o rd e d c c . c c . th ro u g h u r e t h r a i n i t i a l f i n a l c c . P r e s s u re cm. w a te r i n i t i a l f i n a l 0 .2 m m m 0 3 .0 2 .5 4 .0 3 .0 0 .4 0 .2 0 0 4 .5 4 .0 6 .5 4 .5 0 .6 0 .4 8 0 6.0 5 .4 9 .0 8 .0 0 .8 0 .5 8 0 8 .0 7 .0 1 2 .5 11.0 1.0 0 .6 5 0 9 .2 8 .0 15 .5 1 2 .5 1 .2 0 .7 5 10.2 8 . 0 17.5 1 2 .5 1 .4 0 .6 0 10.0 7 .5 1 7 .0 1 2 .0 1 .6 0 .6 0 0 1 0.0 7 .8 17.0 12.3 1 .8 0 .5 5 0 9 .8 6 .5 16.5 9 .8 2 .0 0 .5 5 0 8 .2 8 .0 13 .0 1 2 .5 2 .2 0 .5 3 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 .5 3 0 8 .5 7 .0 13.5 1 1 .0 • ? c - Loss o f f l u i d th ro u g h 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 VESIOAL PRESSURES USING PERFUSATE, pH 3.3 62 P lu id i n j e c t e d cc • Volume i n v e r t i c a l tu b e c c . P lu id r e l e a s e d from b la d d e r th ro u g h u r e t h r a c c . H t. i n mm. r e c o rd e d i n i t i a l f i n a l P r e s s u re cm* w ator i n i t i a l f i n a l * 0 .4 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 .5 8 0 5 .0 5 .0 7 .5 7 .5 1.0 0 .7 3 0 7 .0 4 .0 11.0 6 .0 1.2 0 .5 5 0 6 .9 4 .0 10.5 6 .0 1.4 0 .4 8 0 7 .0 3 .3 11.0 4 .9 1 .6 0 .5 8 0 5 .0 4 .0 7 .5 6 .0 1 .8 0 .6 0 0 5 .7 3 .0 8 .5 4 .0 2 .0 0 .4 5 ? -Jr* 6 .0 3 .0 9 .0 4 .0 2 .2 0 .5 0 0 4 .3 3 .0 6 .5 4 .0 2 .4 0 .5 3 0 4 .3 3 .0 6 .5 4 .0 2 .6 0 .5 5 0 5 .0 3 .7 7 .5 5.5*** 2 .8 0 .5 5 0 5 .0 3 .5 7 .5 5 .0 3 .0 0 .4 5 0 6 .0 6.0 9 .0 9 .0 R ec o rd in g began a t .4 c c . ** Loss o f f l u i d th ro u g h u r e t h r a ; volume e lim i n a t e d unknown. Leakage around th e c a n n u la a t th e p la c e o f i n s e r t i o n i n th e b l a d d e r . C U l Qurv w 5 Q ^ V • (p No. 6201-T, University Bookstore, Los Angeles TABLE XII rat #4— nembutal anesthesia, analysis op KMMOGRAM SHOWING RESULTANT VESICAL PRESSURES USING SALINE PERFUSATE 64 F lu id i n j e c t e d cc • Volume i n v e r t i c a l tu b e c c . F lu id r e l e a s e d from b la d d e r th ro u g h u r e t h r a H t. i n mm. re c o rd e d i n i t i a l f i n a l P r e s s u re cm. w ater i n i t i a l f i n a l 0 .2 0 2 .6 2 .6 3 .5 3 .5 0 .4 0 .2 0 0 5 .2 5 .2 7 .5 7 .5 0 .6 0 .5 5 0 7 .2 7 .2 11.3 11.3 0 .8 0 .6 5 0 9 .5 9 .2 16.0 15.3 1 .0 0 .8 0 0 1 1 .0 1 1 .0 1 9 .5 19.5 1 .2 0 .9 5 0 13.0 1 2 .7 2 5 .0 2 4 .0 1 .4 1 .1 0 15.0 14 .3 3 0 .0 28 .5 1 .6 1 .2 5 0 17.0 1 6 .0 3 5 .5 3 4 .0 1 .8 1 .5 5 0 18.0 17.2 3 8 .5 3 6 .5 2 .0 1 .4 5 0 19.0 18.2 4 1 .8 3 9 .0 2 .2 1 .6 3 0 2 1 .0 2 0 .4 4 8 .5 4 6 .5 2 .4 1.78 0 2 2 .8 2 2 .0 5 5 .0 51 .6 2 .6 1 .9 2 4 .5 2 3 .2 62 .5 5 6 .5 2 .8 1.93 0 .4 2 4 .9 2 2 .0 64.5 51.6 5 .0 1 .7 0 2 2 .0 2 0 .8 51.6 4 7 . 5-5-x- Loss o f f l u i d th ro u g h u r e t h r a ; volume e li m i n a t e d unknown, -îô -x - Leakage o c c u rre d a t th e v e r t i c a l tu b e c a n n u la j u n c t i o n . TABLE XIII 65 RAT #4--NEMBUTAL ANESTHESIA, ANALYSIS OP KYMOGRAM SHOVVING RESULTANT VESICAL PRESSURES USING SALINE PERFUSATE F lu id Volume i n F lu id r e l e a s e d H t. i n mm. P r e s s u re i n j e c t e d v e r t i c a l tu b e from b la d d e r r e c o rd e d cm. w a te r c c . c c . th ro u g h u r e t h r a i n i t i a l f i n a l i n i t i a l f i n a l 0 .2 0 .2 4 0 3 .0 3 .0 4 .0 4 .0 0 .4 0 .2 0 0 5 .0 5 .0 7 .5 7 .5 0 .6 0 .5 3 0 7 .0 7 .0 11.0 1 1 .0 0 .8 0 .6 5 0 9 .0 9 .0 15 .0 15.0 1 .0 0 .7 8 0 1 1 .5 10.0 2 0 .8 17.0 1 .2 1 .0 0 1 3 .0 1 1 .5 2 5 .0 2 0 .8 1 .4 1 .1 5 0 1 5 .0 13.0 3 0 .0 2 5 .0 1 .6 1 .2 0 1 6 .6 13.0 3 4 .5 2 5 .0 1 .8 1.03 0 .2 1 8 .0 13.0 3 8 .5 2 5 .0 2 .0 0 .9 0 .3 1 5 .0 9 .0 3 0 .0 15.0 2 .2 0 .7 8 0 .1 1 4 .0 10.0 2 7 .5 17.0 2 .4 0 .6 5 1 3 .0 9 .0 2 5 .0 15.0 2 .6 0 .5 5 0 11.0 8 .3 19.5 1 3 .5** 2 .8 0 .5 5 0 1 0 .0 7 .0 1 7 .0 11.0 3 .0 0 .4 5 ? 1 0 .0 8 .0 1 7.0 1 2 .5 3 .2 0 .5 3 0 1 0 .0 8 .0 1 7 .0 12 .5 * x - Loss of f l u i d from u r e t h r a ; volume e lim in a te d unknown The an im al was u n d e r l i g h t a n e s t h e s i a and became v e ry a c t i v e . ilLllf é t T O T o.A o . y 1 . 2. u' le No. 62ÜI-T, University Bookstore, Los Angeles TABLE XIV rat #4— decerebrate, ANALYSIS OP KYMOGRAM SHOWING RESULTANT VESICAL PRESSURES USING SALINE PERFUSATE 67 F lu id i n j e c t e d cc • Volume i n v e r t i c a l tube CO . F lu id r e l e a s e d from b la d d e r th ro u g h u r e t h r a H t. i n ram. r e c o rd e d i n i t i a l f i n a l P r e s s u re cm. w a te r i n i t i a l f i n a l 0 .2 0 .2 4 0 3 .0 3 .0 4 .0 4 .0 0 .4 0 .4 3 0 6 .0 6 .0 9 .0 9 .0 0 .6 0 .6 3 0 9 .0 9 .0 15.0 1 5.0* 0 .8 0 .8 0 0 1 1 .5 11.0 2 0 .9 2 0.0 1 .0 1 .0 0 14.0 1 4 .0 2 7 .5 2 7 .5 1 .2 1 .1 5 0 1 6 .0 1 6.0 3 3 .0 3 3 .0 1 .4 1 .3 5 0 1 8 .0 18.0 3 8 .5 3 8 .5 1 .6 1.5 8 0 2 1 .0 2 1 .0 4 8 .5 4 8 .5 1 .8 0 .8 5 0 .4 2 1 .5 8 .0 5 0 .0 12.5** ■ Î I - S l i g h t le a k a g e o c c u rre d a t v e r t i c a l tu b e / c a n n u la j u n c t i o n . R e f le x m i c t u r i t i o n . TABLE XV RAT #4--DECEREBRATE, ANALYSIS OP KYMOGRAM SHOWING RESULTANT VESICAL PRESSURES USING PERFUSATE, pH 3.3 68 F lu id i n j e c t e d c c . Volume i n v e r t i c a l tu b e CO . F l u i d r e l e a s e d from b la d d e r th ro u g h u r e t h r a H t. i n mm. r e c o rd e d i n i t i a l f i n a l P r e s s u r e cm. w a te r i n i t i a l f i n a l 0 .2 0 1 .0 1 .0 0 .5 0 .5 0 .4 ?* 2 .0 2 .0 2 . 5 2 .5 0 .6 9 2 .5 2 .5 3 .0 3 .0 0 .8 9 3 .0 3 .0 4 .0 4 .0 1 .0 9 3 .5 4 .6 5 .0 6 .8 1 .2 0 .4 3 0 6.0 6 .0 9 .0 9 .0 1 .4 0 .5 5 0 7 .5 7 . 5 12.0 12.0 1 .6 0 .6 0 0 8 .0 8 .0 1 2 .5 1 2 .5 1 .8 0 .8 0 0 1 0 .5 1 0 .5 1 8 .0 18.0 2 .0 0 .8 5 0 I I . 5 9 .5 2 1 .0 16.0 2 .2 0 .7 3 ? 1 0 .0 9 .0 1 7 .0 15 .0 2 .4 0 .7 0 ? 1 0 .8 9 .0 1 9 .0 15.0 2 .6 0 .7 3 0 10.8 9 .0 1 9.0 15 .0 2 .8 0 .7 3 0 10.0 9 .5 17.0 16.0 3 .0 0 .8 0 0 1 0 .4 7 .4 18.0 11 .5 3 .2 0 .6 5 ? 9.0 8 .0 1 5 .0 1 2 .5 3 .4 0 .7 0 0 8 .5 7 .0 1 3 .5 1 1 .0 3 .6 0 .8 3 0 10.0 10 .0 17.0 1 7.0 3 .8 0 .9 0 0 1 1 .0 9 .5 1 9 .5 16.0 4 .0 0 .9 0 9 12.3 8 .5 2 3 .0 1 3 .5 4 .2 0 .8 3 ? 11.0 1 0 .0 1 9 .5 17 .0 * Loss of f l u i d th ro u g h u r e t h r a ; volume e l i m i n a t e d unknown. TABLE XVI 69 RAT #4--DECEREBRATE, ANALYSIS OF KYMOGRAM SHOWING RESULTANT VESICAL PRESSURES USING PERFUSATE, pH 3.3 F lu id Volume In F lu id r e l e a s e d H t. i n mm. P r e s s u re i n j e c t e d v e r t i c a l tu b e from b la d d e r re c o rd e d cm. w a te r c c . c c . th ro u g h u r e t h r a i n i t i a l f i n a l i n i t i a l f i n a l 0 .2 — 0 4 .0 4 .0 6 .0 6 .0 0 .4 0 .2 0 0 6 .9 6 .9 1 0 .5 1 0 .5 0 .6 0 .1 8 0 10.0 10.0 1 7 .0 1 7 .0 0 .8 0.7 3 0 13 .0 1 2 .0 2 6 .0 2 2 .0 1 .0 0 .7 8 ?* 13 .0 11.5 2 5 .0 2 1 .0 1 .2 0 .7 3 0 14.0 1 0 .5 2 7 .5 18.0 1 .4 0 .6 8 0 1 1 .0 10.0 1 9 .5 17 .0 1 .6 0 .6 5 ? 1 3 .0 11.0 2 5 .0 1 9 .6 1 .8 0 .7 0 0 1 2 .5 1 0 .5 2 3 .5 18.0 2 .0 0 .6 5 0 1 2 .8 11.0 2 4 .5 19 .5 2 .2 0 .6 8 0 1 2 .0 11.0 2 2 .0 1 9 .5 2 .4 0 .6 3 0 1 2 .8 10.5 2 4 .5 18.0 2 .6 0 .6 0 0 1 1 .5 10.0 2 1 .0 1 7.0 2 .8 0 .6 0 ? 1 1 .3 10.0 2 0 .4 17 .0 3 .3 0 .8 3 0 1 5 .0 13.0 3 0 .0 2 5 .0 * Loss o f f l u i d th ro u g h u r e t h r a volume e lim in a te d unknown. WB 4ND v , ‘x:pèSD--tyî) 4Kq Y îy )9i;vz! ^-TG -Q TrM'iT-rWAçæ# M «■/, W icluV ^L if liiÀ I i 4 # a Œ t e É E Ë r 5-k4i-i4+• ' _ o 0.4. 0.% \ No. O JO l- J, Uiliverait.'. Bookstore, Los Angeles TABLE XVII RAT #5--DECaREBRAT2, ANALYSIS OP KYMOGRAM SHOWING RESULTANT VESICAL PRESSURES USING SALINE PERFUSATE 71 F lu id Volume i n F lu id r e l e a s e d H t. i n mm. i n j e c t e d v e r t i c a l tube from b la d d e r r e c o rd e d c c . immed. 1 m in. th ro u g h u r e t h r a i n i t i a l f i n a l a f t e r a f t e r P re s s u re cm. w a te r i n i t i a l f i n a l i n j i n j 0 .2 ? ** 0 .5 0 .5 1.0 1 .0 0 .4 __ 0 2 .2 2 .2 4 .0 4 .0 0 .6 0 5 .0 3 .0 8 .5 8 .5 0 .8 _ 9 5 .9 3 .5 9 .6 9 .6 1.0 .33 ? 8 .0 4 .5 14.0 7 .5 1 .2 .36 ? 8 .0 4 .6 1 4 .0 7 .5 1 .4 .45 _ ? 8 .5 4 .9 1 5 .0 8 .3 1 .6 .45 0 8 .0 3 .9 1 4 .0 6 . 6 1 .8 .45 ? 7 .5 3 .1 13. 5.6 2 .0 .45 — ? 6 .4 3 .0 1 0 .8 5 .5 * F lu id i n can n u la e / tube j u n c t i o n ** Loss o f f l u i d from b l a d d e r th ro u g h u r e t h r a ; volume unknown. TABLE XVIII 72 RAT #5— DECEREBRATE, ANALYSIS OP KYMOGRAM SHOWING RESULTANT VESICAL PRESSURES USING PERFUSATE, pH 4.52 F lu id i n j e c t e d c c . Volume i n v e r t i c a l tube immed. 1 rain, a f t e r a f t e r i n j . i n j . c c . F lu id r e l e a s e d from b la d d e r th ro u g h u r e t h r a H t. in mm. re c o rd e d i n i t i a l f i n a l P r e s s u re cm. w a te r i n i t i a l f i n a l 0 .2 0 2 .1 2 .1 3 .7 3 .7 0 .4 0 5 .1 4 .8 8 .5 8 .0 0 .6 .45 .42 0 6.9 6.2 1 1 .5 10.4 0 .8 .55 .53 0 9 .0 7 .0 16.0 1 2 .0 1 .0 .60 .53 0 9 .0 7 .5 1 6 .0 1 3 .0 1 .2 .60 .50 ?* 9 .5 7 .0 1 7 .0 12.0 1 .4 .60 .55 9 9 .0 7 .0 1 6 .0 1 2 .0 1 .6 .63 .58 ? 9 .2 7 .0 1 6 .5 12.0 1 .8 .58 .45 0 8 .5 6 .1 15 .0 1 0 .0 2 .0 .50 .42 ? 7 .9 6 . 0 1 3 .7 9 .9 2 .2 .58 .42 ? 8 .2 5 .5 1 4 .5 9 .2 * Loss of f l u i d from b la d d e r ■ th ro u g h u r e t h r a ; volume unknown. TABLE XIX 73 RAT #5--DEGEREBRATE, ANALYSIS OF KYMOGRAM SHOWING RESULTANT VESICAL PRESSURES USING PERFUSATE, pH 8.4 F lu id Volume in i n j e c t e d v e r t i c a l tube CO. immed. 1 min. a f t e r a f t e r i n j . i n j . CO . F lu id r e l e a s e d H t. i n mm. from b la d d e r re c o rd e d th ro u g h u r e t h r a i n i t i a l f i n a l P r e s s u re cm. w a te r i n i t i a l f i n a l 0 .2 — ?* 0 .8 0 .8 1 .5 1 .5 0 .4 ? 2 .3 2 .0 4 .2 3 .6 0 .6 9 3 .0 2 .5 5 .5 4 .5 0 .8 9 4 .0 3 .0 7 .0 5 .5 1 .0 ? 5 .0 4 .0 8 .5 7 .0 1 .2 .36 9 6 .2 4 .5 10.4 7 .6 1 .4 .45 .33 ? 6 .0 4 .5 10 .0 7 .6 1 .6 .48 ? 7 .0 4 .5 12.0 7 .6 1 .8 .45 .33 ? 7 .0 4 .5 1 2 .0 7 .6 2 .0 .40 .33 0 7 .0 5 .0 1 2 .0 8 .5 2 .2 .48 .33 9 8 .0 5 .0 1 4 .0 8 .5 2 .4 .55 .38 ? 6 .2 4 .0 10 .4 7 .0 2 .6 .45 .33 0 7 .2 4 .9 1 2 .5 8 .2 2 .8 .50 .36 9 8 .0 5 .5 14.0 9 .2 * Loss of f l u i d from b la d d e r th ro u g h u r e t h r a ; volume unknown. là: 6.4 û .g f . ^ No. 6201-1, U niversity Bookstore, Los Angeles I- i _ TABLE XX 75 RAT #6--DE0EREBRATE, ANALYSIS OF KYMOGRAM SHOWING RESULTANT VESICAL PRESSURES USING SALINE PERFUSATE F lu id Volume i n i n j e c t e d v o r t i c a l tube c c . immed. 1 m in. a f t e r a f t e r i n j . i n j . F lu id r e l e a s e d H t. i n mm. from b la d d e r re c o rd e d th ro u g h u r e t h r a i n i t i a l f i n a l P r e s s u re cm. w a te r i n i t i a l f i n a l 0 .2 w 0 1 .5 1 .0 3 .0 2 .0 0 .4 0 3 .8 3 .6 6 .5 6 .3 0 .6 0 .3 0 .3 6 0 5 .0 4 .0 8 .5 7 .0 0 .8 0 .4 0 .3 6 ? 6 .5 5 .5 11.0 9 .0 1 .0 0 .4 0.3 3 ? 6 .2 5 .0 1 0 .5 8 .5 1 .2 0 .4 3 0 .3 3 ? 6 .8 5 .0 1 1 .5 8 .5 1 .4 0 .4 5 0 6 .0 4 .5 9 .9 7 .5 1 .6 0 .3 3 9 5 .9 4 .0 9 .8 7 .0 1.8 9 5 .0 3 .0 8 . 5 5 . 5 2 .0 9 4 .5 2 .5 7 .5 4 .5 2 .2 _ 9 5 .0 3 .0 8 .5 5 .5 2 .4 0 .4 0 0 6 .0 4 .5 9 .9 7 .5 TABLE XXI RAT #6--DECEREBRATE, ANALYSIS OF KYMOGRAM SHOWING RESULTANT VESIOAL PRESSURES USING PERFUSATE, pH 4.52 76 F lu id i n j e c t e d c c . Volume i n v e r t i c a l tube immed. 1 m in. a f t e r a f t e r i n j . i n j . F lu id r e l e a s e d from b la d d e r th ro u g h u r e t h r a H t. in mm. re c o rd e d i n i t i a l f i n a l P r e s s u re cm. w a te r i n i t i a l f i n a l * 0 .4 0 1 .5 1 .5 3 .0 3 .0 0 .6 .36 0 4 .5 3 .2 7 .5 5 .6 0 .8 .38 __ ? 5 .0 3 . 5 8 .5 6.0 1 .0 .40 __ ? 5 .2 3 .6 8 .6 6.4 1 .2 .36 ? 4 .2 2 .2 7.4 4 .0 1 .4 .40 ? 5 .5 3 .0 9 .0 5 .5 1 .6 .38 ? 5 .0 3 .0 8 .5 5 .5 1 .8 .42 _ ? 6 .0 2 .1 9 .9 4 .9 2 .0 9 5 .0 3 .0 8 .5 5 .5 2 .2 .40 ? 4 .5 2 .5 7 .5 4 .5 4 c - R ec o rd in g began a t 0 .4 c c . i n j e c t i o n , # æ= 1. o No. 6201-T, Université Bookstore, Los Angeles TABLE XXII 78 RAT #G--DECaREBRATE, ANALYSIS OP KYMOGRAM SHOWING RESULTANT VESICAL PRESSURES USING PERFUSATE, pH 8.4 F lu id Volume i n F lu id r e l e a s e d H t. i n mm. P r e s s u re i n j e c t e d v e r t i c a l tube from b la d d e r r e c o rd e d cm. w a te r c c . immed. 1 m in. th ro u g h u r e t h r a i n i t i a l f i n a l i n i t i a l f i n a l a f t e r a f t e r i n j . i n j . 0 .2 ? 2 .5 2 .5 4 .5 4 .5 0 .4 0 4 .5 4 .2 7 .5 7 .4 0 .6 .38 ? 6 .0 4 .1 9 .9 7 .0 0 .8 .48 ? 7 .5 3 . 6 1 3 .0 6 .3 1 .0 .38 ? 6 .0 4 .0 9 .9 7 .5 1 .2 .38 ? 6 .0 4 .5 9 .9 7 .5 1 .4 .36 ? 5 .8 3 .5 9 .5 6 .0 1 .6 . 50 .38 ? 8 .0 5 .0 14.0 8 .5 1 .8 .33 ? 5 .5 3 .5 9 .2 6 .0 2 .0 .38 ? 6 .0 3 .6 9 .9 6 .3 2 .2 .48 .38 ? 7 .5 4 .5 1 3 .0 7 .5 2 .4 .45 ? 6.5 4 .2 1 1 .0 7 .4 2 .6 .48 ? 6 .2 5 .0 10.5 8 .5 TABLE XXIII 79 RAT #6--DECEREBRATE, ANALYSIS OP KYMOGRAM SHOWING RESULTANT VESICAL PRESSURES USING PERFUSATE, pH 4.52 F lu id i n j e c t e d c c . Volume i n v e r t i c a l tube immed. 1 m in. a f t e r a f t e r i n j . i n j . F lu id r e l e a s e d from b la d d e r th ro u g h u r e t h r a H t. i n mm. re c o rd e d i n i t i a l f i n a l P r e s s u r e cm. w a te r i n i t i a l f i n a l 0 .2 0 1 .5 1 .5 3 .0 3 .0 0 .4 .38 0 4 .6 3 .5 8 .0 6 .0 0 .6 .50 .40 0 6 .5 4 .0 1 1.0 7 .0 0 .8 .45 .40 0 6 .0 3 .5 9 .9 6 .0 1 .0 .45 ? 5 .7 3 .2 9 .5 5 .6 1 .2 .53 .40 ? 7 .0 3 .1 12.0 5 .5 1 .4 .45 ? 6 .0 3 .0 9 .9 5 .5 1 .6 .53 .40 ? 6 .9 3 .2 1 1 .5 5 .6 1 .8 .55 .42 ? 8 .0 3 .0 1 4 .0 5 .5 2 .0 .58 ? 7 .0 3 .1 1 2.0 5 .5 2 .2 .58 .42 9 7 .0 3 .0 1 2 .0 5 .5 2 .4 .45 — ? 6 .0 3 .0 9 .9 5 .5 n as KÊ! 0-^ . d.y I' % _ i• b No. 62Ü1-Ï, U o iv n h it\ Bouk'-ioic, Los Angeles 2_ . O TABLE XXIV 81 RAT #7_.DECEREBRATE, ANALYSIS OP KYMOGRAM SHOWING RESULTANT VESICAL PRESSURES USING SALINE PERFUSATE F lu id Volume I n F lu id r e l e a s e d H t, i n mm. P r e s s u r e I n j e c t e d v e r t i c a l tu b e from b la d d e r r e c o rd e d cm, w a te r 0 0 , immed, 1 m in. th ro u g h u r e t h r a i n i t i a l f i n a l i n i t i a l f i n a l a f t e r a f t e r i n j . i n j . 0 .2 _ 0 3 .8 3 .8 6 .5 6 ,5 0 .4 0 4 ,5 4 ,5 7 .5 7 ,5 0 ,6 .42 .42 0 7 .0 7 ,0 1 2 ,0 1 2 .0 0 .8 ,60 .60 0 9 .4 9 .4 1 6 ,9 1 6 .9 1 .0 .75 .75 0 12.0 12.0 2 2 .5 2 2 .5 1.2 .83 .78 ? 1 3.0 1 2 .5 2 5 .0 2 4 .0 1.4 .88 .80 ? 14 ,0 12.0 2 7 .5 2 2 .5 1 ,6 .88 .80 ? 1 4 .0 12 ,2 2 7 .5 2 3 .0 1,8 .86 .68 ? 1 3 ,5 1 1 ,0 2 6 .5 2 0 .3 2 ,0 .86 .73 ? 1 3 .5 11 ,5 2 6 .5 2 1 ,5 2 .2 ,65 ,45 9 13,5 6 ,5 2 6 .5 1 1 .0 2 .4 , 50 .36 9 8 ,5 5 ,9 1 5 .0 9 .7 2 .6 .45 ? 7 .2 5 ,0 12 ,4 8 .5 2 .8 .42 .40 0 7 ,0 6 .9 1 2 ,0 11,6 TABLE XXV 82 RAT #7--DEGEREBRATE, ANALYSIS OP KYMOGRAM SHOWING RESULTANT VESICAL PRESSURES USING PERFUSATE, pH 4.52 F lu id Volume i n F lu id r e l e a s e d H t. i n mm. i n j e c t e d v e r t i c a l tu b e from b la d d e r r e c o rd e d c c . immed. 1 min th ro u g h u r e t h r a i n i t i a l f i n a l a f t e r a f t e r i n j i n j P r e s s u re cm. w a te r i n i t i a l f i n a l 0 .2 — ? .9 1 .0 1 .7 2 .0 0 .4 9 3 .0 3 .0 5 .5 5 .5 0 .6 9 5 .0 5 .1 8 .5 8 .6 0 .8 0 7 .0 7 .0 1 2.0 1 2 .0 1 .0 .40 .40 0 9 .8 7 .0 1 7 .5 12.0 1 .2 .60 .42 9 9 .0 7 .0 1 6 .0 12.0 1.4 .50 .42 ? 9 .9 6 .2 1 7 .9 1 0.5 1 .6 .60 .3 8 ? 8 .9 8 .0 15.6 14.0 1 .8 .50 .48 0 9 .0 5 .5 16.0 9 .0 2 .0 .60 .36 9 7 .5 7 .0 1 3 .0 12.0 2 .2 .44 .44 0 1 0 .0 6 .9 1 8 .0 11.6 2 .4 .63 .42 ? 8 .9 6 .2 15.8 10.5 2 .6 .50 .40 ? 9 .0 5 .9 16.0 9 .8 Ë: trpM i' 1 1 1 XJtV y a O O .V 0 .% V ■ J L - Kt No. ^)2U1-T, Uiiiveiaity Uookstort, I.os Ange)e TABLE XXVI RAT #7--DEGEREBRATE, AÜALY8IÜ OP KYMOGRAM BLOWING RESULTANT VESIGAL PRESSURES USING PERPUSATE, pH 9.1 84 F lu id Volume i n i n j e c t e d v e r t i c a l tube c c . immed. 1 m in. a f t e r a f t e r i n j . i n j . F lu id r e l e a s e d H t. i n irim. from b la d d e r r e c o rd e d th ro u g h u r e t h r a i n i t i a l f i n a l P re s s u re cm. wa t e r i n i t i a l f i n a l 0 .2 ? 2 .0 2 .0 3 .6 3 .6 0 .4 _ ? 3 .6 3 .8 6 .3 6.5 0 .6 .3 6 .36 0 6 .0 6 .0 9 .9 9 .9 0 .8 .45 .45 9 7 .4 7 .0 12.7 1 2 .0 1 .0 . 50 .50 ? 8 .0 7 .5 14.0 13.0 1 .2 .53 .4 8 ? 1 0 .0 7 .5 1 8 .0 1 3 .0 1 .4 .60 .50 ? 9 .8 7 .5 1 7.5 1 3 .0 1 .6 .60 .50 ? 9 .0 7 .7 16.0 1 3 .2 1 .8 .60 .50 9 9 .1 7 .0 16.3 1 2 .0 2 .0 .60 .48 ? 7 .8 7 .5 13.5 13.0 TABLE XXVII 85 RAT #7--DECEREBRATE, ANALYSIS OF KYMOGRAM SHOWING RESULTANT VESICAL PRESSURES USING PERFUSATE, pH 4.52 F l u i d i n j e c t e d cc • Volume i n v e r t i c a l tube immed. 1 m in. a f t e r a f t e r i n j . i n j . F lu id r e l e a s e d from b la d d e r th ro u g h u r e t h r a H t. i n mm. r e c o rd e d i n i t i a l f i n a l P r e s s u r e cm. w a te r i n i t i a l f i n a l 0 .2 0 3 .5 3 .5 6 .0 6 .0 0 .4 .38 .38 0 6 .1 6 .0 10 9 .9 0 .6 .45 .42 0 7 .2 6 .5 1 2 .5 1 1 .0 0 .8 .53 .50 ? 8 .0 7 .6 1 4 .0 1 3 .1 1 .0 .55 .48 ? 8 .3 7 .0 14.8 1 2 .0 1 .2 .60 .48 ? 8 .8 6 .5 1 5 .5 1 1 .0 1.4 .48 .45 9 7 .0 6 .4 1 2 .0 10 .8 1 .6 .50 .48 0 7 .5 7 .0 13.0 1 2 .0 1 .8 .60 .45 ? 9 .0 6 .5 1 6 .0 11.0 2 .0 .55 .50 9 8 .0 6 .9 1 4 .0 1 1 .5 l- w , m m I S JHj LîTm îfti No. 6201-T, University Bookstore, Los Angeles TABLE XXVIII RAT #8--DEGEREBRATE, ANALYSIS OF KYMOGRAM COMPARING VESICAL PRESSURES USING PERPUSATE, pH 5.88 AND ISOSMOLAR SALINE PERPUSATE 87 F lu id Volume i n F lu id r e l e a s e d i n j e c t e d v e r t i c a l tu b e from b la d d e r c c . immed. 1 m in. th ro u g h u r e t h r a a f t e r a f t e r i n j . i n j . H t. i n mm. r e c o rd e d i n i t i a l f i n a l P r e s s u re cm. w a te r i n i t i a l f i n a l SaTine 0 .2 0 2 .2 2 .2 4 .0 4 .0 0.4 0 5 .5 5 .5 9 .0 9 .0 0 .6 .42 .42 0 8 .5 8 .0 1 5 .0 1 4 .0 0 .8 .55 .53 0 11.0 1 0 .0 2 0 .3 18.0 1 .0 .63 .60 0 12 .1 1 1 .5 2 2 .9 2 1 .5 1 .2 .83 .45 0 14.9 9 .9 3 0 .0 1 7 .9 1.4 .68 .63 0 1 3 .0 1 2 .0 2 5 .0 2 2 .5 1 .6 .78 .42 ? 1 5 .0 9 .0 3 0 .5 1 6 .0 B u ffe r 0 .2 S o ln . pH 5.88 0 3 .5 3 .5 6 .0 6 .0 0 .4 0 5 .5 5 .5 9 .0 9 .0 0 .6 .38 .38 0 7 .5 7 .0 13.0 12.0 0 .8 .50 .48 0 9 .0 8 .5 1 6 .0 15 .0 1 .0 .73 .38 ? 12.8 7 .3 2 4 .8 1 2 .5 1 .2 .60 .53 0 11.0 1 0.0 2 0 .3 18.0 1.4 .71 .3 6 ? 1 3.0 6 .9 2 5 .0 11 .5 1 .6 .55 .55 0 1 0.0 9 .0 1 8 .0 1 6 .0 .fT Ï No. 6201-T, U niversity Took-store, Los Angeles 1 -Z., TABLE XXIX 89 RAT #8— DECEREBRATE, AmLYBIS OP KYMüGRAM COMPARING VEBICAL PREBBURES USING PERFUSATE, pH 9.1 AND ISOSMOLAR SALINE PERFUSATE F lu id i n j e c t e d c c . F lu id r e l e a s e d H t. i n mm. from b la d d e r re c o rd e d immed. 1 m in. th ro u g h u r e t h r a i n i t i a l f i n a l a f t e r a f t e r Volume in v e r t i c a l tu b e i n j i n j . P r e s s u r e cm. w a te r i n i t i a l f i n a l S a lin e ' 0 . È 0 3 .1 3 .1 5 .5 5 .5 0 .4 0 5 .5 5 .5 9 .0 9 .0 0 .6 .38 .36 0 7 .2 6 .5 12.4 11.0 0 .8 .48 .45 0 9 .0 8 .2 1 6 .0 1 4 .5 1 .0 .60 .55 0 1 1 .0 1 0 .0 2 0 .3 1 8.0 1 .2 .71 .36 ? 1 2 .4 6 .5 2 3 .5 1 1 .0 1 .4 .53 .48 0 1 0 .0 9 .0 1 8 .0 16.0 1 .6 .71 .36 ? 1 3 .0 6 .5 2 5 .0 1 1.0 B u f f e r, pH 9 .1 b '.T — — 0 3 .1 3 .1 5 .5 5 .5 0 .4 0 5 .8 5 .0 9 .6 8 .5 0 .6 .36 .36 0 7 .0 6 .8 1 2 .0 11.5 0 .8 .45 .42 0 9 .0 8 .0 1 6 .0 14.0 1 .0 .60 0 ir 1 0 .0 _ 1 8 .0 1.2 .78 .40 9 1 4 .5 8 .0 2 9 .0 1 4 .0 1 .4 .68 0 1 3 .0 10.0 2 5 .0 18 .0 1 .6 .90 .38 ? 16.0 7 .5 3 3 .0 1 3 .0 1.8 .58 .50 0 1 1 .0 9 .5 2 0 .3 17.0 2 .0 .95 .45 9 17. 9 .0 3 6 .5 16 .0 ir Not r e c o rd e d î-'Wàt0]? fesalÆn0;,.p 1 ± h rl-h :L .j ThltUt. I 0 ^ 0 < f f ! • k No. O20l-'\, l.'iiivcrsit,' Buokitorc, Los Angeles 2,Û i-tf- 3 . A- TABLE XXX 91 RAT #8--DEGEREBRATE, ANALYSIS OF KYMOGRAM COMPARING VESICAL PRESSURES USING PERFUSATE, pH 2. 18 AND ISOSMOLAR SALINE1 PERFUSATE F lu id i n j e c t e d c c • Volume i n v e r t i c a l tube immed. 1 m in. a f t e r a f t e r i n j . i n j . F lu id from throu; r e l e a s e d b la d d e r gh u r e t h r a H t. i n mm. re c o rd e d i n i t i a l f i n a l P re s s u re cm. w a te r i n i t i a l f i n a l S a lin e 0.È 0 2 .7 2 .7 5 .0 5 .0 0 .4 _ _ 0 6 .2 6 .0 10.5 9 .9 0 .6 .4 0 .38 0 8 .2 8 .0 1 4 .5 14.0 0 .8 .53 .50 0 1 0 .6 1 0 .0 19.2 1 8 .0 1 .0 .68 .68 9 1 3.5 8 .7 2 6 .5 1 5 .4 1 .2 .53 .50 0 11.0 10.2 2 0 .5 1 8 .5 1 .4 .63 .36 9 1 2 .8 7 .3 2 5 .0 1 2 .5 1 .6 . 60 .50 ? 11.8 10 2 2 .0 18.0 1 .8 B u f f e r , 0.É .60 pH 2.1 8 .33 ? 0 1 2 .0 3 .8 7 .0 3 .8 2 2 .5 6 .5 12.0 6 .5 0 .4 0 6 .7 6 .5 11.5 11.0 0 .6 .42 .42 0 9 .0 8 .0 16.0 1 4.0 0 .8 .55 .50 0 1 1 .0 10.5 2 0 .3 1 9 .0 1.0 .60 .42 9 1 2 .0 8 .2 2 2 .5 1 4 .5 1 .2 .60 .38 9 11.5 8 .0 2 1 .5 1 4 .0 1 .4 .58 .36 9 11.2 7 .6 2 0 .6 1 3 .0 1 .6 .58 .36 9 11.5 7 .5 2 1 .5 1 3 .0 1 .8 .58 .36 9 1 1.5 7 .5 2 1 .5 1 3 .0 X sa; ( 3 . oo'J Plùl^- No. 6201-1, U niversity Bookstore, Los Angeles 3-4 TABLE. J>ec.e,,ebn:c +e. fei--~u.soJe.. To+0-I cc. Ivi1+;Cl.I loss D(=. l=-1 u..; d... D.-1 b b le:s M1::.·h.1.~1+;cvis "f\-<::SSU.\--€... u.+ d ,-·, bble. "F'..-<:-s.<.u.1-e o...+ ~ ,c+u.;._, -l-10\/\ AO.a. ph .... + I ' '• (', :qebr-o.1 c n--i e (>...¥\ Co""'c:: l \....L s. l0V1.S "Re..+# iYI j e.C +eq a~ l} l ':...:. :· II ' I \.',~·-~--C?t-~c:...e.. o~ -pre- s..su...1-e ln~ec.+ ,·on .., u.'"'""' be ... I cc . · ""' 1 . I r -t- \.A.I c. e vt._ -.1~1e <.>..v,c.\ r\ ... ec;..~Llre 1'\LlVVI b<" r- -,,u....,..,be1- /cc. ... l"'t1cx-... YV"\f!!!. CL\."\ .. bla_dcl . .,. ..... S\>\,,' VJC +-!'.:'>- '"Lvif:- l1..tev1ce ll c\ J 60. s.e IMj. -i--neo.....V\ ~o...v11e Yo...v>~r"'. of (_")\.-- ll \"""V"Y''e c. VY<. wo._ +e...- .\ ..... b ..... e.. 0... .\- -\--o"">e ..\-c,-,~ c.c. '"' \ :....."' "'-\.q..' ,·...., +-s .. ' i"" ·-- ......... ~"" -- 2. S"-\,·,.,e ( 1) 2...0 {)' 'i \ \ .o 3 I ,5- 0 c I (p , ( (1,0 - 2.. I. CJ 0 C> S \I~\ -----~-.. --. . So..1.me ( -..) ;i...o 1·6 2._<;' s l. ,, c 0 0 ;2(,_, '3 )__~~-Ci -- 2. ·1 ' s.- CJ ( SI•~ h+ .. h I qh -Ke I"- I'- o.. +, ov, o~ c~e-1:- .... u..sc ...-- VYJu.:<:,cle) Ac_;d pH 1.0!»:"(3 2..o 0 0 0 0 c c 0 0 Co c qrc:.0--\- -I ?. I ('l.. 'I -- 10.:z.. 'i (~) -::>...'18' \ 0 CJ.) c.,o..,+1-a.ci-,ovi Of'. l:. p \,., ,· V1c+e r--, ,, ... Sa_\,'.,,,e (<I) .:l_.O \, b L'i. ~- 2.. I , () () c .)_O 3 l'j . .,;· -- ..)_(.0 0 (_~, st,~.._, t 3 So.\~e (3) l_.O I· 2.. (/,:-,- 2.. 1, 0 0 0 I I. 2_ s·- 11.0 - 17. .s-- c C' Y"Y\ode1i-c1..l..e 1<e.l o.. 'fC- o.. +-10Y1 oF <le+.- u.,._ o I-' VV1 ..... ,..cle I Ac.1J .?\.-\ -o.:. ['i .)._ 0 2.0 'i. 'ii I t f; c c_; 'i c 0 c C) '.~t ...-eo-...\.-· -5. 7r,, l 0 u...) h, "h c...ovit-...-a.cf- (0·.,,.., Of- '.i, p \.., ~VlC +er-·, )( --~--·--" Lt Sc-.\ ~e 0 I. \( I . :;' so.o 0 c ( o. s-s-- {) 0 s-0 c no"' e I T< e I a. i<. n.-lc ' 'e--vi C-•f'.- d e.+ru.. s.o .- Irv\ LL SC.le I Act cl PH 3-~ ( ... 1. 'il' O.'\-- 2_,<;'" 4 ..<. 2- 0 0 '::\.(c2_ ). 's- -- s . ci D C• 'V\.o vi £. - :Lo. 0 lot.LJ ! 0 ,_,_, t"'e..lo....I" 0-...>+i'o"' o~ "'r h1 nc..\-c \-' .. \\el"'-·1'-'~-\,m-, of- J E. -1 r<-< '- o <-- VYlt-tSC(C.:-' I Acd n 1--\ 3.~ (s 1-'ls 1.0 :i..::,-,o 2.. (.I () (_; :i..::,-. 0 c 0 c s I (~ht - 7, ~- lo l.Ll l D <..L.J n" [o. f. LL+-< c'v> Of'. "'\~h~,,,c-\-P 1-· ) ·'',1'"' t :;- Sc.l""'e l1) :1.. 0 0 2- (. c l 3 ,,,- n 0 l l I 1.0 - ( ~~. (_) c c SI 1 ~,P..+- ·'~: 'Re\o. i<- 0-.+, Cw--. oF &e,t-,_.u.~Ol-' VYiu..S.C ( C I f.k,J pf-\ +sJ..(>' .l.O (' 2- I 1- 0 .q ). . 0 c 0 IS"', );' ( ::, .-/ I -1 · c 0 0 VV1ad...e,....a...1--e. + 3.0 ~ O LU h ;"t.1-, C0vi+ >--a...c.:\--t OV1 oF- splrir'vic.+.-e...- . CoV\+,....o..d-ioVl OF J. e.-\-1-<...t.S. () ... vv1 Ll_ 5=.c[e I TSa.~ pH ~A (~ .2_.0 0 'l. I, .s,- q .Lj .~- 0 0 ·7' Cf ( ' :,;- 1 ·1_ .c c 'YI O vt e. - .1. I in, q h \o u..J r-clc....)C Cl.-t-< 61.o~ u (- ~ [-' h ·, V'>C + e r · lo So..l~e (.1) 2.0 0 '6 I\, 0 '°' 3,C 0 C) 'i ?: I ~- \/ ,:,,- (; L' ~l.qh+- 12 e.. I <'-"'f-"- +-( L"V1 c+ Jc_t-r--<A.SO t-' v'y1 LLSC le I 4c.ccl pf-I i>°)_ (1 1..0 o.r 't h- -7 ::; !, - C) 0 ~.lc:S '"14 Cf,"( c (' l .4 2-. Io'-'-' h~9h C. .. ovi+..-(Lo;..+< t) v1 s F \." ~,1C+c: ...... - Y'l.-ovi.c - cf- ... Cc.>-vctr <LC•+< u vi ,, f- & e.+-r- L._-1,._ ..f..("\ r--' I B<Lse n[--1 H (.3) 20 0.2.... +s 9 ':'./ s.- 0 (..) 9 .H' 4, ~-- - If, D 0 C.J Vi..cV\e + \. o<o h 1q h lou..1 \-"C'. lo...,<.(\ ... + l C> V) 0 (- 5._, pl, ,· ,_.., c+t: r--. -Rel "-\C lL t l (TV') C' f- c..l et:·1--u.. s. o .... \,~yt.u_~C'.lt":)} f-tc;J. rH +s:i.(4 .2..o (. 0 q.o (., :,, 0 0 0 t I . _;;- q,,.- - 14-. c ,, 0 '"YV\..oJe ..--o.. l,e +- t.4 l lcw htri h c.c vi+ ra..c. +-1 c'·v1 of- Sf\,; l.VJC +-c >-", C· 7 S,.1,;..,e (L~ 2.0 [. 2- ;:1..s.o s 2.:::,- 0 0 ;;{(, _-,,- ;:u,-. o - l. ( '~- 0 0 'VI. 0 V\ c: 12(:' ! C.'"--¥- o .. +- ( u·.,..1 o~ cl t;; + \---<.....J... s.o ...--- y"Y\,.A.-J,._~(_ le_ I Ac;J. PH 4.Sl('.l. 1...0 o. 2. :J... 0 ~- '2..· "'- ,;i I 'i ."\ s.- I, -i - ( <c' c I:-;, 4 ~:- (~' c_; --~ I/· '1 \l\D V\ e... - I. 41 lo u .. l [ CLU \-eh.._/(, o..+ < ~'-• -, Dt'- .s {"l' ~,,c_+e...-, C .... ov1 f-v--o..cJ- t ci v> 0 (.... J E'.+-r---L.t S(', 1-~ v">1LLS.C(~ I Bo..~e, ?H 'l I Qi) 2,..D 0.2 ::;, s- s- .2' s- 4 2. lC·O ~ ''" - I~-. 0 I Iv .'j ,;- llo. u - 1i' 0 V\CV\e - 7 O<c, !<119 l, I ou.J :--eJ CL.\C !l._ + l ·"·H. c""f:-- ""'f\,' ,~.c.J "',..-. ((EI CL'{ LL .... ' 6-V\ cf- J.c+<--~< s.o...- ~-vi.USC ( e ·, f-\c;J. p\-\ '\-D('l 2- 0 Q, 'if 1+ 0 :3 I. 5-.,- 3 i.s- 1-.,:,. "'' 11.c - t4 .'l l !._,-' '2.. 14. () - It, 0 \/)OV\e_ - 7' I I cu...' l C' u...' rt: lcqc_ <.<...-t· 1 o '' cF- ""Pi.-,~,,c+-e...-. g "!. "=:iO'"::.'y"Y'!ol a,,_ 0 C> '.:>"'-\""'te (\) \.Ip I . "2.. 3 o.o 0 () 2. I .0 ::.. C' ''3, '2,o, c ::,,o, s - "r"'-o~e.-c>.k l<clu..'(. "1: l l)-V\. 0 f- t_Le+-.._...._,4.._s.ct- vv11.c. St: 'e I f\c..-1~ 'p!+ s- ~i; (:i' I. lo I· 0 :i.. ,,-, 0 () 0 2... I.,) c 0 )_L\ ''t 2.1+ 'ti - 2.~-. 0 ""<>tie~ a. 4--e -3 07 I o<..U h '"{ l-1 C <h<... +ro..C.\--t L,·,., Cf- sp h ,·v1c~c './ LSo~Molt> r 0 W\oJe .. a.....\-c '.':.>...l;,,,e (?:, [.I,. (, '2.. i9 0 0 0 2.. I. cl c :L."' ' ?s 23. s- - 2.S'"' c c (rct._+ <--a._ C + ( 'o- VJ o{. & !:_-' { '-u.....S.OY ..,.-,,1<-LSC It' ' B<>-se. , pt! '1·1 f1 \.!,, l ·2. :::i. ?,. s~ c 0 .2.. I. D l_1 (.) .:_,I, '-' :2...'l.o - .:-;-~. C) Yvl oJ <" r-":h~. + 3. I h.~h \ 0 u..l r-e.\ CL..-1- a_+ ' o· n "(.:.. s. \-' l ) L 0 .-<,_ 1 C +--e r --, tI::,os.,,..,o ltt ...- '.)_ \,, .s- c (.) 3: I , s.- c ;_:.,' s- -~- '=-' s- \!>·' o,d. e. ...-"-k Su..l~ne Isl \.(,, [, 0 0 ~ :::. ' C: - G(::.: le;.. "f-- o__ +- t c \-) cc... '-{f'_{ \--u__SO r ~-v1 u. S.-<: lr · 1 l+c-(J pft d, ts' (1.) 1,. 6 i .G c "-\- - c I.._~ :__I, ~ :.._ c'\, L -- - V'1 oc\ ~,. ,,_ -l-<" o. 3 s- I G cu lo u.J ' c:.:::. r_:., l--") '"- 'l(_°_+c_ 'r' ' ;L.:.... . s- v ~· c - _._ ·-- ' -~ -- y e. \ (!_ K ::..t._ -t-- t (_.';.·..._ Cf- -..... ~ .. CHAPTER IV D is c u s s io n OP EXPERIMENTAL RESULTS As can be seen i n F ig u re 6 , norm al m i c t u r i t i o n d id o c c u r i n d e c e r e b r a t e r a t s and was s i m i l a r to t h a t d e s c r ib e d as o c c u r r in g i n c a t s . S a lin e was in tr o d u c e d i n t o th e b la d d e r a t 2 m in u te i n t e r v a l s so t h a t s u f f i c i e n t tim e was allo w e d f o r a d a p t a t i o n of th e v e s i c a l m u s c u la tu r e . W ith each i n j e c t i o n o f f l u i d i n t o th e b l a d d e r , t h e r e was a s te a d y r i s e i n v e s i c a l p r e s s u r e o f a b o u t 2 cm. w a te r . Up to 1 .8 c c . i n j e c t i o n volume, a s l i g h t f a l l of p r e s s u r e of a p p ro x im a te ly 1 - 2 cm. w a te r o c c u rre d d u rin g th e i n t e r v a l s betw een i n j e c t i o n s . Above t h a t i n j e c t i o n volum e, th e p r e s s u r e r o s e more s t e e p l y , i n c r e a s i n g o v er 3 tim es t h a t r e s u l t i n g from p re v io u s e q u a l i n c r e m e n ts . The f a l l i n p r e s s u r e which took p la c e d u r in g th e i n t e r v a l s i n d i c a t e d th e o c c u rre n c e o f a d a p t a t i o n , or a r e a d ju s tm e n t of v e s i c a l tone i n re s p o n s e to i n c r e a s e d volume. This a d a p t a t i o n was d e f i n i t e l y g r e a t e r a t h ig h e r volum es. When th e c r i t i c a l volum e, o r th e l i m i t o f t o l e r a n c e was r e a c h e d , d i s t e n s i o n o f th e b la d d e r w a ll i n i t i a t e d a s t i m u l a t i o n of s t r e t c h r e c e p t o r s which r e f l a x l y p roduced a c t i v e v e s i c a l c o n t r a c t i o n s , r e s u l t i n g i n r e f l e x m i c t u r i t i o n . From th e r e s u l t s o b ta in e d from 2 r a t s u n d e r nem butal a n e s t h e s i a , i t can be seen t h a t norm al m i c t u r i t i o n d id n o t o c c u r and n e m b u tal a n e s t h e s i a was f o r t h a t r e a s o n u n s u i t a b l e 95 f o r m i c t u r i t i o n s t u d i e s . In r a t # 4 , (see F ig u re 11, t r i a l 1) i n which a n e s t h e s i a was f a i r l y deep , th e b la d d e r showed c o m p a r a tiv e ly l i t t l e a d a p t a t i o n , even a t h ig h p r e s s u r e s . R e fle x m i c t u r i t i o n d id n o t o c c u r, b u t r a t h e r s l i g h t d r i b b l i n g took p l a c e , as a r e s u l t o f th e e x tre m e ly h ig h p a s s iv e f o r c e e x e r te d on th e s p h i n c t e r by th e i n t e r n a l v e s i c a l p r e s s u r e . A second t r i a l on th e same r a t , as can be seen i n F ig u re 11, shov/ed q u i t e a d i f f e r e n t r e a c t i o n . The v a r i a b i l i t y of re s p o n s e no d o u b t can be e x p la in e d by v a r i a t i o n s i n th e d e p th o f a n e s t h e s i a ; as th e a n e s t h e s i a wore o f f , t h e r e was no lo n g e r a d e p r e s s io n o f s t r e t c h r e c e p t o r s , e n a b lin g a c t i v e b la d d e r c o n t r a c t i o n s to o c c u r, w ith r e f l e x em ptying o f th e v i s c u s . R at #3 (se e F ig u re 9) showed a somewhat d i f f e r e n t r e a c t i o n u n d e r nem b u tal a n e s t h e s i a , b u t h e r e a g a in , d e p th o f a n e s t h e s i a was p ro b a b ly th e i n f l u e n c i n g f a c t o r . S in ce i t h a s been d e m o n stra te d i n smooth m u scles from v a r io u s s o u rc e s t h a t d e c re a s e i n c o n t r a c t i o n s and d e c r e a s e i n tonus o c c u r i n re sp o n se to s o l u t i o n s of a c id pH, and s in c e i t h a s been d e m o n stra te d t h a t i n c r e a s e i n c o n t r a c t i o n s and i n c r e a s e i n tonus o ccu r i n re s p o n s e to s o l u t i o n s of a l k a l i n e pH, one m ig h t e x p e c t s i m i l a r e f f e c t s on th e smooth m u s c u la tu re of th e v e s i c a l w a ll. Denny-Brown and R o b e rtso n (19.33), showed t h a t i n c a t and man, th e b la d d e r s p h i n c t e r s and d e t r u s o r m uscle have a r e c i p r o c a l r e l a t i o n s h i p ; t h a t i s , i f th e to n e of th e b la d d e r 96 was h ig h , th e to n e o f th e s p h i n c t e r s was low, and v ie a v e r s a . They d e m o n stra te d t h a t th e i n t e r n a l s p h i n c t e r co u ld n o t open v /ith o u t th e p re se n c e of v e s i c a l cunli'ac Lion and c l o s u r e o f th e s p h i n c t e r was c o n c u r r e n t w ith v e s i c a l r e l a x a t i o n . The f in d i n g s o f Langworthy, Reeves and Tauber (1934) c o n firm ed th e s e view s. J .P . Evans (1 9 3 6 ), r e p o r t e d a c o n s t a n t d is c h a r g e o f im p u lses to th e e x t e r n a l s p h i n c t e r w h ile th e b la d d e r p r e s s u r e was low. This a c t i v i t y was i n h i b i t e d f o r a b r i e f moment b e f o r e the l i q u i d p a s se d from th e u r e t h r a . I n th e l i ^ t o f a l l th e s e o b s e r v a t i o n s , one m ight e x p e c t t h a t as a r e s u l t of p e r f u s i o n w ith a c i d s o l u t i o n , the smooth m uscle of th e w a ll o f th e u r i n a r y b l a d d e r would show d e c r e a s e d to n e , and d e c re a s e d c o n t r a c t i o n s . I f a r e c i p r o c a l r e l a t i o n s h i p e x i s t s betw een th e d e t r u s o r m uscle and th e b la d d e r s p h i n c t e r , th e n i n c r e a s e d s p h i n c t e r to n e would be e x p e c te d u n d e r th e s e c o n d i t i o n s . As a r e s u l t of th e s e e f f e c t s , i t would seem t h a t th e d e c r e a s e d tone of th e d e t r u s o r m u s c u la tu re would r e s u l t i n l e s s r e s i s t e n c e to s t r e t c h , t h e r e f o r e g r e a t e r r e l a x a t i o n ; g r e a t e r r e l a x a t i o n th e n would r e s u l t i n g r e a t e r volume c a p a c i t y a t c o m p a r a tiv e ly lo w er p r e s s u r e s . I n t u r n w ith th e c o n c o m ita n t i n c r e a s e d s p h i n c t e r tone l e s s lo s s o f f l u i d th ro u g h th e u r e t h r a v/ould be e x p e c te d . Thus, f o llo w in g th e same r e a s o n i n g , i n t r o d u c i n g a f l u i d o f low pH i n t o th e b l a d d e r would cau se r e l a x a t i o n o f th e d e t r u s o r m uscle and c o n t r a c t i o n o f th e b la d d e r s p h i n c t e r and 97 would r e s u l t i n a l a r g e a c c u m u la tio n o f f l u i d . With in c r e a s e d r e l a x a t i o n , i n i t i a t i o n of c o n t r a c t i o n of the b l a d d e r m uscle by p a s s iv e d i s t e n s i o n would be d e la y e d u n t i l d i s t e n s i o n c au sed by c o m p a r a tiv e ly l a r g e r volumes r e s u l t e d i n a p o w e rfu l, com plete em ptying o f th e b la d d e r a t a h ig h p r e s s u r e . C o n v e rse ly , p e r f u s i n g th e b l a d d e r w ith a l k a l i n e p e r f u s a t e would cause i n c r e a s e d tone and i n c r e a s e d c o n t r a c t i o n s o f th e d e t r u s o r m uscle w ith d e c r e a s e d to n e o f th e s p h i n c t e r . As a r e s u l t of th e e f f e c t s of h ig h pH, i t v\Tould seem t h a t th e i n c r e a s e d tone o f th e d e t r u s o r m u s c u la tu re would r e s u l t i n g r e a t e r r e s i s t a n c e to s t r e t c h t h e r e f o r e g r e a t e r c o n t r a c t i o n ; g r e a t e r c o n t r a c t i o n would th en r e s u l t in low er volume c a p a c i t y a t c o m p a r a tiv e ly h i g h e r p r e s s u r e s . With the c o n c o m ita n t d e c re a s e d s p h i n c t e r to n e one would e x p e c t g r e a t e r fre q u e n c y of lo s s o f f l u i d th ro u g h th e u r e t h r a . While th e p r e s s u r e s r e s u l t i n g from th e e f f e c t of i n c r e a s e d b la d d e r tone cau sed by a l k a l i n e pH would be h ig h a t low volum es, one would n o t e x p e c t t h a t th e s e p r e s s u r e s would be as h ig h as the p r e s s u r e a t e l i m i n a t i o n a t t a i n e d by th e b la d d e r i n re sp o n se to a c id p e r f u s i o n s in c e th e f r e q u e n t lo s s of f l u i d would p e rm it o n ly a s m a ll volume a c c u m u la tio n i n a l k a l i n e p e r f u s i o n . While th e above d i s c u s s i o n has c o n s id e re d p r i m a r i l y th e d i r e c t e f f e c t of th e pH o f p e r f u s a t e s on th e d e t r u s o r m uscle w ith th e se c o n d a ry , o r i n d i r e c t , e f f e c t on th e s p h i n c t e r m uscle th ro u g h r e f l e x r e c i p r o c i t y which e x i s t s betw een th e b la d d e r m u s c u la tu re and th e b l a d d e r s p h i n c t e r , i t i s q u i t e 98 p o s s i b l e t h a t pH m ig h t e f f e c t th e b l a d d e r s p h i n c t e r d i r e c t l y . I f t h i s be th e c a s e , th e d i r e c t i n f l u e n c e o f pH on the s p h i n c t e r m uscle m ig h t o b scu re e x p e c te d r e c i p r o c i t y . I n th e p r e s e n t i n v e s t i g a t i o n , a t o t a l of 7 r a t s were u sed to compare e f f e c t s o f v a r io u s p e r f u s a t e s on th e a c t i v i t y of th e u r i n a r y b la d d e r and th e m i c t u r i t i o n r e f l e x . A t o t a l of 26 p e r f u s i o n t r i a l s were ru n on th e s e r a t s , 1 1 o f the p e r f u s i o n s b e in g w ith s a l i n e , 11 w ith b u f f e r m ix tu re s of a c id pH, and 4 w ith b u f f e r m ix tu re s o f a l k a l i n e pH. Because of th e v a r i a t i o n found in th e e x p e r im e n ta l r e s u l t s , i t was im p o s s ib le to i s o l a t e any s i n g l e c r i t e r i o n on which to base c o n c l u s io n s , and i t was d i f f i c u l t to e v a l u a t e r e s u l t s and p r e s e n t ev id e n c e in q u a n t i t a t i v e v a l u e s . An a tte m p t was made to c o n s id e r a l l th e im p o r t a n t c r i t e r i a , and a summary o f th e a n a l y s i s o f e x p e r im e n ta l r e s u l t s i s p r e s e n t e d i n T able XXXI. I n e v a l u a t i n g th e e f f e c t s of p e r f u s a t e s of v a r io u s pH on the u r i n a r y b la d d e r a l l of th e f a c t o r s l i s t e d i n th e t a b l e must be c o n s id e r e d . As p r e v i o u s l y d i s c u s s e d , one m ight e x p e c t low er p r e s s u r e s i n p e r f u s i o n v/ith a s o l u t i o n of a c i d pH up to a c e r t a i n l i m i t , and h i g h e r p r e s s u r e s in p e r f u s i o n v/ith s o l u t i o n s of a l k a l i n e pH. T his was t e s t e d as one c r i t e r i o n on which to b a s e c o n c lu s io n s and was e x p r e s s e d as th e a l g e b r a i c mean d i f f e r e n c e of th e p r e s s u r e between th e b la d d e r p e r fu s e d w ith s a l i n e and th e same b l a d d e r p e r fu s e d w ith a c i d o r betv/een s a l i n e and b ase p e r fu s e d b l a d d e r a t th e e x p e r im e n ta l p o i n t s . 99 i . e . same i n j e c t i o n volum es. However, th e o c c u rre n c e o f d r i b b l i n g i n some c a s e s and n o t i n o t h e r s c o m p lic a te d the i n t e r p r e t a t i o n and s i m p l i c i t y of p r e s e n t a t i o n . I n i n s t a n c e s where l e s s d r i b b l i n g o c c u rre d i n a c i d p e r f u s i o n as compared to s a l i n e o r a l k a l i n e p e r f u s i o n , (se e F ig u re 13) g r e a t e r p r e s s u r e s were r e c o r d e d . The g r e a t e r b la d d e r c o n te n ts i n a c id p e r f u s i o n as compared to s a l i n e and a l k a l i n e p e r f u s i o n i n t h i s c a se would seem to a c c o u n t f o r th e g r e a t e r p r e s s u r e , hence o b s c u rin g th e r e l a x a t i o n e f f e c t , so t h a t to say sim p ly t h a t p e r f u s i o n v/ith a c i d s o l u t i o n i n t h e s e c a s e s r e s u l t e d i n h i g h e r p r e s s u r e s would n o t o n ly be m is le a d in g b u t would be an in c o m p le te d e s c r i p t i o n of r e s u l t s . L ikev/ise, i n i n s t a n c e s where a h i g h e r fre q u e n c y o f d r i b b l e s o c c u rre d i n a c i d p e r f u s i o n , and low p r e s s u r e s were r e c o rd e d i t a g a in would be m is le a d in g to s t a t e sim p ly t h a t low er p r e s s u r e s were m a in ta in e d , and g r e a t e r r e l a x a t i o n was e f f e c t e d by a c i d p e r f u s i o n w ith o u t c o n s id e r i n g th e i n f l u e n c e of f l u i d l o s s . The h ig h tone of the b l a d d e r w a ll e x p e c te d i n p e r f u s i o n w ith s o l u t i o n o f a l k a l i n e pH p r e s e n t s a s i m i l a r d i f f i c u l t y . High b la d d e r to n e would a llo w l e s s b l a d d e r volume, produce low s p h i n c t e r tone and f r e q u e n t lo s s of f l u i d th ro u g h th e u r e t h r a . C o n se q u e n tly , a g ra p h ic r e p r e s e n t a t i o n of b la d d e r p r e s s u r e m ight a t f i r s t g la n c e be m is le a d in g i n t h a t p r e s s u r e s r e c o rd e d m ight be below th o se of e i t h e r a c id or s a l i n e . From th e f o re g o in g d i s c u s s i o n i t would seem n e c e s s a r y 100 th e n to c o n s id e r a l l th e f a c t o r s l i s t e d i n th e t a b l e i n e v a l u a t i n g th e e f f e c t o f a c id o r a l k a l i n e p e r f u s a t e s on th e u r i n a r y b l a d d e r . With a l l of th e s e f a c t o r s i n mind th e n , i t was found t h a t a l k a l i n e p e r f u s a t e was 1 0 0 ^ e f f e c t i v e i n c a u s in g I n c r e a s e d b la d d e r to n e , w ith a r e c i p r o c a l l y d e c re a s e d s p h i n c t e r to n e . Acid p e r f u s a t e was found to be 10Q% e f f e c t i v e i n c a u s in g d e c re a s e d b l a d d e r to n e , w ith 64^ showing r e c i p r o c a l l y i n c r e a s e d s p h i n c t e r to n e , and 36^ showing d e c re a s e d s p h i n c t e r to n e . These e f f e c t s co u ld be a t t r i b u t e d to th e h y d ro g e n -io n c o n c e n t r a t i o n o f th e p e r f u s a t e r a t h e r th an th e osm otic p r e s s u r e d i f f e r e n c e s in c e s a l i n e s o l u t i o n s , is o s m o tic w ith th e b u f f e r e d p e r f u s a t e s o f th e v a r io u s pH’ s d id n o t have th e same e f f e c t , t h a t i s th e b la d d e r re sp o n d e d to a g iv en b u f f e r e d pH of p e r f u s a t e i n a c o n s ta n t manner r e g a r d l e s s o f th e osm otic p r e s s u r e o f the p e r f u s a t e . While a m a j o r i t y of th e a c i d p e r f u s i o n t r i a l s showed i n c r e a s e d s p h i n c t e r to n e , a f a i r l y h ig h p e r c e n ta g e (36^) showed th e o p p o s ite e f f e c t . P erhaps the low pH of th e p e r f u s a t e e f f e c t e d a l s o th e s p h i n c t e r m uscle i n c a u s in g r e l a x a t i o n , i n which c ase th e r e c i p r o c i t y o f th e b l a d d e r w a ll and s p h i n c t e r u r e t h r a may n o t h o ld t r u e . On th e o t h e r hand th e e f f e c t may be e x p la in e d by b i o l o g i c a l v a r i a b i l i t y which i s c e r t a i n l y a p ro m in en t c h a r a c t e r i s t i c of a l l p h y s i o l o g i c a l p r o c e s s e s . For a s t a t i s t i c a l l y v a l i d c o n c lu s io n , i t would be n e c e s s a r y to r e p e a t th e e x p e rim e n ts many t i m e s . CHAPTER V SUMMARY AND CONCLUSIONS U sing i s o t o n i c s a l i n e , S o r e n s e n ’ s b u f f e r s o l u t i o n s o f a c i d and a l k a l i n e pH, and s a l i n e is o s m o tic wi th th e b u f f e r m i x t u r e s , th e i n t a c t u r i n a r y b la d d e r of th e r a t was p e r f u s e d , and th e r e a c t i o n a r y v e s i c a l a c t i v i t y was r e c o rd e d kym ographic - a l l y th ro u g h a w r i t i n g tam bour. R e s u lts were o b ta in e d from 8 d e c e r e b r a t e r a t s , 2 o f w hich had been p r e v i o u s l y a n e s t h e t i z e d w ith n em b u tal and th e b la d d e r had b een p e r fu s e d v/ith i s o t o n i c s a l i n e and a c id s o l u t i o n s to o b serv e 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 p r i o r to d e c e r e b r a t i o n . I n th e f i r s t s e r i e s of e x p e rim e n ts u s in g 4 r a t s , 5 s o l u t i o n s were i n j e c t e d i n t o th e b la d d e r f o r com parison of b la d d e r a c t i v i t y : i s o t o n i c s a l i n e 0.85%; and S o r e n s e n ’ s b u f f e r s o l u t i o n s , pH 1 .0 5 and pH 3 .3 2 . I n th e second s e r i e s o f ex p e rim e n ts u s in g 3 r a t s , th e b la d d e r was p e r fu s e d v/ith i s o t o n i c s a l i n e , and S o r e n s e n ’ s b u f f e r m i x t u r e s , pH 4 .6 2 , pH 8 . 4 , and pH 9 .1 i n a c o m p arativ e s tu d y of b la d d e r a c t i v i t y . I n th e l a s t e x p e rim e n t u s in g 1 r a t , th e b la d d e r was p e r fu s e d w ith b u f f e r s o l u t i o n , pH 5.88 and is o s m o la r s a l i n e ; b u f f e r s o l u t i o n , pH 9 .1 and is o s m o la r s a l i n e ; and b u f f e r s o l u t i o n , pH 2 .1 8 and is o s m o la r s a l i n e . The e x p e rim e n t was run 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 in g 102 d i f f e r e n t b u f f e r s was due p r i m a r i l y to d i f f e r e n c e s i n pH or due to d i f f e r e n c e s in osm otic p r e s s u r e s o f th e s o l u t i o n s . The u r i n a r y b la d d e r o f d i f f e r e n t r a t s showed d i f f e r e n t t o l e r a n c e l e v e l s to th e same p e r f u s a t e , m i c t u r a t i n g a t d i f f e r e n t volumes and d i f f e r e n t p r e s s u r e s ; b u t th e v a lu e s were f a i r l y c o n s i s t e n t f o r th e same r a t . I n th e r a t u n d e r deep nem b u tal a n e s t h e s i a th e u r i n a r y b la d d e r showed g r e a t e r volume and g r e a t e r p r e s s u r e t o l e r a n c e th a n th e b la d d e r o f th e d e c e r e b r a t e a n im a l. No com plete m i c t u r i t i o n r e f l e x was o b ta in e d i n d i c a t i n g a d e p r e s s i o n o f s t r e t c h r e c e p t o r s w i t h i n th e v e s i c a l m u s c u la tu r e . 771 th d e c re a s e d a n e s t h e s i a , th e b la d d e r showed a c t i v e v e s i c a l c o n t r a c t i o n s and t o l e r a t e d l e s s volume and l e s s p r e s s u r e . In p e r f u s i n g th e b la d d e r w ith s o l u t i o n s o f v a r io u s pH’ s , i t was found t h a t a l k a l i n e p e r f u s a t e was IOO7 0 e f f e c t i v e i n c a u s in g in c r e a s e d b la d d e r to n e , v/hile a c i d p e r f u s a t e was 100/d e f f e c t i v e i n c a u s in g d e c re a s e d b la d d e r to n e . This e f f e c t i s i n ag reem en t w ith t h a t found i n e x c is e d s t r i p s of smooth m uscle from v a r io u s s o u r c e s . I n p e r f u s i n g th e b la d d e r w ith a l k a l i n e b u f f e r s , a 100^ r e c i p r o c a l r e l a t i o n s h i p betw een th e s p h i n c t e r and th e b la d d e r m u sc u la tu re was e v i d e n t , t h a t i s i n a l l t r i a l s , a l k a l i n e p e r f u s i o n caused i n c r e a s e d b la d d e r to n e and d e c re a s e d s p h i n c t e r t o n e . In p e r f u s i n g th e b la d d e r w ith a c id b u f f e r s , a 64% r e c i p r o c a l r e l a t i o n s h i p betw een th e s p h i n c t e r and th e b la d d e r 103 m u s c u la tu r e was e v i d e n t , w h ile a 36^ n o n - r e c i p r o c a l r e l a t i o n s h ip was i n d i c a t e d , i n t r o d u c i n g th e p o s s i b i l i t y of a d i r e c t e f f e c t o f th e h y d ro g e n -io n c o n c e n t r a t i o n on th e s p h i n c t e r m u s c le . These e f f e c t s on th e to n e o f th e b l a d d e r were a t t r i b u t e d to the h y d r o g e n -io n c o n c e n t r a t i o n o f th e p e r f u s a t e s , r a t h e r th a n th e osm otic p r e s s u r e d i f f e r e n c e s s in c e s a l i n e s o l u t i o n s , is o s m o tic w ith th e b u f f e r e d p e r f u s a t e s o f th e v a r io u s pH’ s d id n o t have th e same e f f e c t as th e s e b u f f e r e d p e r f u s a t e s . BIBLIOGRAPHY A. BOOKS Gannon, ?/.B., and A. R o sen b lu etîi, Autonomic N e u r o - E f f e c to r S y stem s, New Y ork: The M acm illan Company, 1937. 2^29 pp. D’Amour, P . E . , and P. B lood, Manual f o r L a b o ra to ry Work i n Mammalian P h y s io lo g y . Chicago: U n i v e r s i t y o f Chicago P r e s s , 1Ù4F. B. PERIODICAL ARTICLES A nderson, E . , and W. Haymaker, "G lucose T o le ra n c e i n D e c e re b ra te d R ats A f t e r R e l a t i v e l y Long S u r v i v a l , " P r o c . S o c . E x p t l . B i o l . M ed., 7 0 :8 6 -9 0 , 1949. B a r r in g to n , P . J . P . , "The Nervous Mechanism o f M i c t u r i t i o n , " Q u a r t . J . E x p t l . P h y s i o l . , 8 :3 3 -7 1 , 1914. : "The R e l a t i o n o f th e Hind B ra in to M i c t u r i t i o n , " B r a in , 4 4 :2 3 -5 3 , 1921. : "The Nervous C o n tro l o f M i c t u r i t i o n , " Med. S c i . A b s t. R e v ., 5 :2 1 6 -2 1 , 1921. : "The C e n t r a l Nervous C o n tro l of M i c t u r i t i o n , " B r a in , 5 1 :2 0 9 -2 0 , 1928. : "The Component R e fle x e s o f M i c t u r i t i o n i n th e C a t. I and I I . , " B r a i n , 5 4 :1 7 7 -8 8 , 1931. : " L o c a li z a ti o n o f P a th s S u b se rv in g M i c t u r i t i o n i n th e S p in a l Cord o f th e C a t," B r a i n , 5 6 :1 2 6 -4 8 , 1933. : "The Component R e fle x e s o f M i c t u r i t i o n i n th e C a t, I I I , " B ra in , 6 4 :2 3 9 -4 3 , 1941. II B o z le r, E . , "Uber d i e Fragc des T o n u s s u b s t r a t e s , " Z t s c h r . v e r g l . P h y s i o l . , 7 :4 0 7 -3 5 , 1928. : "An A n a ly s is o f th e P r o p e r t i e s of Smooth M u sc le ," Cold S p rin g H arbor Symposia Q u a n t. B i o l . , 4 :2 6 0 -6 6 , 1936. 105 : " E l e c t r i c a l S t i m u l a t io n and C onduction o f E x c i t a t i o n i n Smooth M u sc le ," J . P h y s i o l . , 1 2 2 :6 1 4 -2 3 , 1938. : "A ction P o t e n t i a l s and C onduction o f E x c i t a t i o n i n M u sc le ," B i o l . Sym posia, 3 :9 5 -1 0 9 , 1941. : " in f lu e n c e of E s tro n e on th e E l e c t r i c a l C h a r a c t e r i s t i c s and th e M o t i l i t y o f U te r in e M u sc le ," E n d o c rin o lo g y , 2 9 :2 2 5 -2 7 , 1941. Denny-Brown, D . , and E.G. R o b e rtso n , "On th e P h y sio lo g y of M i c t u r i t i o n , " B r a i n , 5 6 :1 4 9 -9 0 , 1933. : "The S t a t e o f th e B la d d e r and I t s S p h i n c t e r s i n Complete T ra n s v e rs e L e sio n of S p i n a l Cord and Cauda E q u in a ," B r a i n , 5 6 :3 9 7 -4 6 2 , 1933. D ixon, W .E., "The I n n e r v a t i o n of th e P r o g ’ s S tom ach," J . P h y s i o l . , 2 8 :5 7 -7 5 , 1902. E l l i o t , T .R ., "The I n n e r v a t i o n o f th e B la d d e r and U r e t h r a , " J . P h y s i o l . , 3 5 :3 6 7 -4 4 5 , 1906. Evans, C .L ., "The P h y sio lo g y of P l a i n M u sc le ," P h y s io l. R e v s ., 6 :3 5 8 -9 8 , 1926. Evans, C .L ., " S tu d ie s on th e P h y sio lo g y of P l a i n M uscle. I I . The Oxygen Usage o f P l a i n M uscle, and i t s R e l a t i o n to Tonus, £ . P h y s i o l . , 5 8 :2 2 -3 2 , 1923. Evans, C .L ., and S.W.P. U n d e r h i l l , " S tu d ie s on th e P h y sio lo g y o f P l a i n M uscle. I . The e f f e c t o f a l t e r a t i o n o f h y d ro g e n - io n c o n c e n t r a t i o n on th e tone and c o n t r a c t i o n s of p l a i n m u s c le ," J . P h y s i o l . , 4 8 :1 -1 3 , 1923. Evans, J . P . , " O b se rv a tio n s on N erves o f S upply to th e B lad d er and U r e th ra o f th e C at, IVith a Study of T h e ir A c tio n P o t e n t i a l s , " J . P h y s i o l . , 8 6 :3 9 6 -4 1 4 , 1936. F i s c h e r , E. " V e r te b r a te Smooth M u sc le ," P h y s i o l . R e v s ., 2 4 :4 6 7 -9 0 , 1944. G a sse r, U .S ., and A.V. H i l l , "The Dynamics o f M uscular C o n t r a c t i o n ," P r o c . Roy. S o c . B, 9 6 :3 9 8 -4 3 7 , 1924. G e llh o rn , E . , "The S e n s i t i v i t y o f th e S t r i a t e d M uscle to Changes i n pH," Am. J . P h y s i o l . , 1 0 5 :3 5 3 -5 7 , 1933. 106 Hammett, F - , "The I n t e s t i n a l Mechanism P r i m a r i l y S tim u la te d by Sodium C a rb o n a te ," J . P h y s i o l . , 5 5 :309, 1921. K olb, L .C ., and O.R. Langw orthy, "A C om parative Study of the E f f e c t s o f th e B a r b i t u r a t e s , E th e r and B ulbocapnine on M i c t u r i t i o n , " J . P h arm acol. E x p t l . T herap. 63: 10 8 -2 1 , 1938. K untz, A ., and G. Saccomanno, "S ym pathetic I n n e r v a t i o n o f th e D e tr u s o r M u sc le ," J . U r o l . , 5 1 :5 3 5 -4 2 , 1944. L a n d is , E.M ., "The C a p i l l a r y Blood P r e s s u r e i n Mammalian M esen tery As D eterm ined By M i c r o - i n j e c t i o n M ethod," Am. J . P h y s i o l . , 9 3 :3 5 3 -6 2 , 1930. Langw orthy, O .R., and C.B. B rack, "The E f f e c t o f P regnancy and th e Corpus Luteum Upon V e s ic a l M u sc le ," t o . J . O b s t e t . G ynecol. , 37: 1 2 1 -6 , 1939. Langw orthy, O .R ., D.L. R eeves, and S .S . Tauber, "Autonomic C o n tro l of th e U rin a ry B l a d d e r , " B r a i n , 5 7 :2 6 6 -9 0 , 1934. Langw orthy, O .R ., and E .L . Murphy, "Nerve Endings i n th e U r in a ry B la d d e r ," J . Comp. N e u r o l. , 7 1 :4 8 7 -5 1 0 , 1939. Lew is, L .G ., O.R. Langw orthy, and J .E . D e e s, "B ladder A b n o rm a litie s Due to I n j u r y of Motor Pathways i n th e Nervous S y stem ," J.A.M .A. 105:2126, 1935. MacDonald, A .D ., and E.D. McCrea, "O b se rv a tio n s on th e C o n tro l o f th e B la d d e r. The E f f e c t s of Nervous S t i m u l a t io n and o f D ru g s ," Q u a r t . J . E x p t l . P h y s i o l . , 2 0 :3 7 9 -9 1 , 1930. S te w a r t, C .C ., "On th e Course o f Im p u lses to and From th e C a t ’ s B la d d e r ," J . P h y s i o l . , 2 :1 8 2 -2 0 1 , 1899. T a l a a t , M ., " A ffe re n t Im p u lses i n th e Nerves S u p p ly in g th e U r in a ry B la d d e r ," J . P h y s i o l . , 8 9 :1 -1 3 , 1937. Windl e , W .F., and W, M inear, "A P ro c e d u re For D e c e r e b r a tin g th e Rat by th e Anemia M ethod," The A nat. R ec. , 5 7 :1 - 5 , 1933. W inton, F . 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Creator Gallo, Gloria (author)

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

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