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UBC Theses and Dissertations

Acute ligation of the portal vein Johnstone, Frederick Robert Carlyle 1954

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ACUTE LIGATION OF THE PORTAL VEIN  by  FREDERICK ROBERT CARLYLE JOHNSTONE  A THESIS SUBMITTED IN PARTIAL FULFILMENT OF THE REQUIREMENTS FOR THE DEGREE OF MASTER OF SCIENCE i n the Department of ANATOMY  We a c c e p t t h i s t h e s i s as conforming t o t h e s t a n d a r d r e q u i r e d from c a n d i d a t e s f o r the degree o f MASTER OF SCIENCE.  Members o f the Department o f Anatomy THE UNIVERSITY OF BRITISH COLUMBIA OCTOBER, 195k  Ill A B S T R A C T A review of the l i t e r a t u r e been p r e s e n t e d .  on l i g a t i o n o f t h e p o r t a l v e i n has  A b r i e f s u r v e y o f the l i t e r a t u r e  on the l i g a t i o n o f  h e p a t i c v e i n s and t h e h e p a t i c a r t e r y has been i n c l u d e d . t h a t w h i l e t h e r e i s no disagreement  t h a t the r e s u l t  The r e v i e w r e v e a l s  o f sudden a c u t e  l i g a t i o n o f the p o r t a l v e i n i n dogs i s i n e v i t a b l y d e a t h , agreement as t o the cause o f d e a t h .  the  there i s d i s -  The main t h e o r i e s a r e  (i)  that  e x s a n g u i n a t i o n i n t o t h e s p l a n c h n i c v a s c u l a r bed o c c u r s , ( i i ) t h a t t h e o f b l o o d i s i n s u f f i c i e n t t o cause d e a t h , i m p l i c a t e d , the " t o x i c " theory.  loss  and t h a t o t h e r f a c t o r s must be  The s p e c i e s d i f f e r e n c e i n t h e e f f e c t s  of  l i g a t i o n a p p e a r s t o l i e i n the degree o f p o r t o - s y s t e m i c venous anastomoses.  The e x p e r i m e n t s d e s c r i b e d i n t h i s t h e s i s were performed w i t h t h e dog as t h e e x p e r i m e n t a l a n i m a l .  A measurement o f t h e d e c r e a s e i n  c i r c u l a t i n g b l o o d volume f o l l o w i n g l i g a t i o n o f t h e p o r t a l v e i n , u s i n g t h e " l a b e l l e d " r e d c e l l method, was made. consecutive estimations r e d c e l l method.  I t was c o n s i d e r e d t h a t v a l i d  o f b l o o d volume c o u l d be made u s i n g the " l a b e l l e d "  W i t h 11 d o g s , 30 m i n u t e s a f t e r  portal vein ligation,  t h e d e c r e a s e amounted t o 51.9% o f the o r i g i n a l b l o o d v o l u m e .  The  measurement o f the n o r m a l s p l a n c h n i c v a s c u l a r b l o o d volume was made u s i n g 10 dogs.  T h i s amounted t o 21,1% o f the c i r c u l a t i n g b l o o d volume, o r  1 7 . 7 m l . p e r k i l o g r a m body w e i g h t .  As the t o t a l v a s c u l a r bed had been  reduced b y the e x c l u s i o n o f t h i s s p l a n c h n i c p o r t i o n , the s m a l l e r c i r c u l a t i n g b l o o d volume was r e q u i r e d t o s e r v e a s m a l l e r v a s c u l a r a r e a ,  and i t was  c o n s i d e r e d t h a t the t r u e d e c r e a s e i n c i r c u l a t i n g b l o o d volume was 44.8$.  therefore  I t was c o n s i d e r e d t h a t t h i s amount o f b l o o d l o s s was n o t adequate  IV to account for the inevitability of death, or the short period, of survival (79.7 minutes) when compared to the effects of bleeding comparable quantities of blood, or bleeding to comparable levels of blood pressure. Haematocrit estimations were made on the systemic arterial blood and portal venous blood before and after ligation of the portal vein.  There was a significant decrease i n the systemic arterial  haematocrit, and rise i n the portal venous haematocrit.  By the injection  of latex into the portal vein of 3 dogs, the main porto-systemic venous anastomoses were found to occur i n relation to the vagus nerves at the lower end of the oesophagus. Other porto-systemic venous anastomoses were of minor importance.  I t was not possible to influence the outcome  of acute portal vein ligation by splenectomy, or by antibiotics under the conditions of the experiments.  I TABLE OF CONTENTS Page Introduction H i s t o r i c a l survey  1 2  Acute l i g a t i o n o f p o r t a l v e i n  2  Chronic o b l i t e r a t i o n of p o r t a l v e i n  6  Intermittent occlusion of portal vein  7  Species difference  7  O c c l u s i o n o f p o r t a l v e i n i n man  9  L i g a t i o n of hepatic veins  13  L i g a t i o n o f hepatic artery  XU  Purpose o f i n v e s t i g a t i o n  1?  Experimental  20  E x p e r i m e n t a l method  20  1. G e n e r a l  20  2. B l o o d p r e s s u r e  21  3. B l o o d samples  22  l i . Haematocrit e s t i m a t i o n  22  J>. A c u t e l i g a t i o n o f p o r t a l v e i n  22  6. E s t i m a t i o n o f b l o o d volume  23  7. M i x i n g o f a c t i v a t e d r e d c e l l s w i t h c i r c u l a t i n g r e d c e l l s  2k  8. D e t e r m i n a t i o n o f communications between t h e p o r t a l and s y s t e m i c venous c i r c u l a t i o n  25  9. Measurement o f s p l a n c h n i c b l o o d volume  26  II TABLE OF CONTENTS continued  Page  Observations 1. Acute l i g a t i o n o f p o r t a l v e i n  28 ,,  28  (a) L e n g t h o f s u r v i v a l  28  (b) O b s e r v a t i o n s on b l o o d p r e s s u r e  29  2 . B l o o d volume e s t i m a t i o n s  31  3 . E s t i m a t i o n s o f s p l a n c h n i c b l o o d volume  36  k. H a e m a t o c r i t e s t i m a t i o n s  38  5. S i t u a t i o n o f p o r t o - s y s t e m i c venous anastomoses  hi  6. E x h i b i t i o n of a n t i b i o t i c s  hh  General discussion Summary  •  U6 52  Tables - I to IX  5.4-62  Figures - I to V(b)  63-69  ACUTE LIGATION OF THE PORTAL VEIN  INTRODUCTION L i g a t i o n o f t h e p o r t a l v e i n , w h i c h a t one time was o n l y performed b y t h e e x p e r i m e n t a l p h y s i o l o g i s t , has now become o f c l i n i c a l i m p o r t a n c e . W i t h the i n c r e a s i n g scope o f a b l a t i v e c a n c e r o p e r a t i o n s , few s t i l l command r e s p e c t .  Of t h e s e , the p o r t a l v e i n i s o n e .  structures  When d i s e a s e  has s p r e a d t o i n v o l v e i t s w a l l , r e m o v a l o f t h e d i s e a s e d segment i s n o t c o n t e m p l a t e d , f o r u n t i l r e c e n t l y l i g a t i o n was t h o u g h t t o be f a t a l .  This  b e l i e f i s b a s e d f o r t h e most p a r t on e x p e r i m e n t a l work w i t h t h e d o g . r e v i e w o f the l i t e r a t u r e w h i c h f o l l o w s i n c l u d e s a l s o the e f f e c t s  The  of chronic  o b l i t e r a t i o n , o f p a r t i a l o b s t r u c t i o n and o f l i g a t i o n o f t h e b r a n c h e s o f t h e p o r t a l v e i n , f o r though t h e r e s u l t o f t h e s e i n c o m p l e t e l i g a t i o n s d i f f e r s m a r k e d l y from t h a t o f sudden a c u t e l i g a t i o n , the e x p l a n a t i o n s must be related.  The  l i v e r i s r e m a r k a b l e i n d r a w i n g i t s b l o o d s u p p l y from two  s o u r c e s , w h i c h j o i n w i t h i n t h e parenchyma, and d r a i n b y common venous o u t l e t s i n t o the i n f e r i o r vena c a v a .  The one s o u r c e , t h e h e p a t i c  s u p p l i e s w e l l oxygenated b l o o d a t a h i g h p r e s s u r e j  the o t h e r ,  artery, the p o r t a l  v e i n , s u p p l i e s r e l a t i v e l y p o o r l y oxygenated b l o o d a t a low p r e s s u r e .  But  t h e p o r t a l v e i n s u p p l i e s n e a r l y two t h i r d s o f t h e t o t a l q u a n t i t y o f b l o o d d e l i v e r e d t o the  liver.  When the l i t e r a t u r e i s r e v i e w e d c o n c e r n i n g t h e r e s u l t s o f i n t e r f e r e n c e w i t h the s u p p l y o f b l o o d b y t h e h e p a t i c a r t e r y t h e r e seems t o be l i t t l e correspondence w i t h t h e e f f e c t o f l i g a t i o n o f the p o r t a l v e i n .  But i t i s , nevertheless,  necessary to consider these r e s u l t s , f o r  the  common d i s t r i b u t i o n o f t h e b l o o d from t h e s e two s o u r c e s b r i n g s them i n t o relation.  HISTORICAL SURVEY  1.  A c u t e L i g a t i o n o f the P o r t a l V e i n Ore i n 1856 d u r i n g a n i n v e s t i g a t i o n i n t o t h e f o r m a t i o n o f b i l e  f i r s t r e c o r d e d t h e f a c t t h a t sudden o b l i t e r a t i o n o f the p o r t a l v e i n r e s u l t e d i n t h e d e a t h o f t h r e e dogs w i t h i n an h o u r . Schiff  C l a u d e B e r n a r d (1859) and  (1863) i n d e p e n d e n t l y f o u n d t h e same r e s u l t .  Bernard postulated  cause o f d e a t h as a b l o o d y c o n g e s t i o n o f the i n t e s t i n e s . t i e s a l i g a t u r e , d e a t h i s t h e i n e v i t a b l e consequence. t o t h r e e - q u a r t e r s o f an hour l a t e r . understand.  " I f one s u d d e n l y  The a n i m a l d i e s h a l f  The mechanism o f d e a t h i s easy t o  A l l t h e b l o o d t e n d s t o accumulate i n t h e v e s s e l s o f t h e  t i n e , where the a r t e r i e s away i m m e d i a t e l y .  the  intes-  c a r r y i t without cease, without i t being taken  The b r a i n and o t h e r organs become e x s a n g u i n a t e d and t h e  animal d i e s , i n f a c t ,  o f anaemia."  Schiff  (1863) b y t y i n g a l l the v e i n s  o f the l i v e r c l a i m e d t o suppress b i l i a r y s e c r e t i o n , and he c o n s i d e r e d t h a t the a c c u m u l a t i o n o f b i l e i n t o x i c a t e d t h e a n i m a l .  He i n j e c t e d b l o o d from  the r i g h t h e a r t i n t o t h e d o r s a l lymph sac o f a l i v e r l e s s f r o g . circulation failed,  h i s r e f l e x e s were l o s t , and d e a t h ensued.  a n o r m a l a n i m a l d i d n o t produce t h i s r e s u l t .  The f r o g ' s B l o o d from  These two t h e o r i e s ,  e x s a n g u i n a t i o n , and t h a t w h i c h supposes t o x i c s u b s t a n c e s  that of  t o accumulate i n  the b l o o d , have c o n t i n u e d t o have t h e i r a d h e r e n t s t o t h e p r e s e n t  time.  S c h i f f ' s t h e o r y appeared t o r e c e i v e s u p p o r t from the work o f Tappeiner (1873).  I n the r a b b i t he e s t i m a t e d t h a t 16.2$ o f t h e b l o o d was t r a p p e d i n t h e intestines  after  t h e p o r t a l v e i n had been l i g a t e d , b u t p r o b a b l y l i t t l e  w e i g h t can be a t t a c h e d t o h i s f i g u r e s , f o r he e s t i m a t e d t h e t o t a l b l o o d volume t o be o n l y h-S6% o f i t s body w e i g h t , and t h a t 3.08$ o f i t s w e i g h t as b l o o d c o u l d be b l e d w i t h o u t d e a t h o c c u r r i n g .  Nevertheless,  t h i s paper  was much q u o t e d , and i n 1877 Lauteribach i n P h i l a d e l p h i a t h o u g h t he had d i s p o s e d o f anaemia as t h e cause o f d e a t h because ( l ) t h e a r t e r i a l b l o o d p r e s s u r e r i s e s i m m e d i a t e l y f o l l o w i n g l i g a t i o n , (2) t h e a n i m a l s never show convulsions p r i o r to death,  (3) l i g a t u r e o f t h e h e p a t i c v e i n s , w h i c h p r o -  duces an analogous s t a s i s i s n o t f o l l o w e d b y the same symptoms. ;  As an a l t e r n a t i v e ^ he m a i n t a i n e d t h a t an unknown p o i s o n c a u s e d death^and t o p r o v e t h i s t h e s i s i n j e c t e d 3 c c . o f b l o o d from t h e v e i n o f dogs i n t o f r o g s .  portal  A l l d i e d i n three hours, i n a fashion s i m i l a r to  t h e dogs w h i c h had t h e i r p o r t a l v e i n s l i g a t e d .  T h i s work was q u i c k l y r e f u t e d b y Mouselraan and L i e n a u x i n 1885, who i n a c a r e f u l s e r i e s o f e x p e r i m e n t s ,  after  l i g a t i o n o f the p o r t a l v e i n  ( l ) i n j e c t e d p o r t a l v e i n blood i n t o frogs without r e s u l t s ,  (2) c o u l d m a i n -  t a i n t h e dog a l i v e l o n g e r , and r e s t o r e i t s p r e s s u r e w i t h b l o o d t r a n s f u s i o n , (3) c o u l d p r o l o n g l i f e b y l i g a t i n g t h e f e e d i n g a r t e r i e s , s u r v i v a l b y r e l e a s i n g the l i g a t u r e ,  (U) c o u l d a l l o w  (5) showed t h a t complete l i g a t i o n o f  the h e p a t i c v e i n s o n l y was e x t r e m e l y h a r d t o p e r f o r m .  A c c o r d i n g l y they  m a i n t a i n e d t h a t d e a t h was i n d e e d due t o d i m i n u t i o n o f t h e q u a n t i t y o f c i r c u l a t i n g b l o o d , and a l s o t o "an i n s u f f i c i e n c y i n t h e q u a l i t i e s o f t h e b l o o d , t h a t i s , i t s oxygen o r c a r b o n d i o x i d e c o n t e n t . "  T h e i r work  r e c e i v e d s u p p o r t from C a s t a i g n e and B n d e r i n 1899, who a l s o showed t h a t e  - h L i f e was p r o l o n g e d b y t r a n s f u s i o n and b y l i g a t i o n i n t h i s c a s e , a o r t a above t h e c o e l i a c a x i s .  "We have been s t r u c k ,  o f the  i n a l l our e x p e r i -  e n c e s , b y t h e f a c t t h a t t h e aniraals d i e a b s o l u t e l y as i f t h e y had been bled."  C a s t a i g n e and Bender a l s o quote N e t t e r i n 1881*. as o r i g i n a t i n g the  s u g g e s t i o n t h a t t o x i n s a r e produced i n t h e b o w e l and t h e s e , u n a b l e t o be d e t o x i f i e d b y the L i v e r , cause d e a t h .  They f e l t t h a t t h e y had d i s p r o v e d  t h i s hypothesis of Netter.  I n 1913 Neuhof took up the i n v e s t i g a t i o n a g a i n , and n o t i c e d t h a t t h e a c u t e engorgement o f t h e i n t e s t i n e s and t h e manner o f d e a t h were a n a l a gous t o d e a t h from s h o c k .  He was t h e f i r s t t o contemplate l i g a t i o n o f t h e  p o r t a l v e i n as a s u r g i c a l p r o c e d u r e .  U n t i l 1932 no o t h e r e f f o r t  than  T a p p e i n e r ' s seems t o have been made t o measure t h e amount o f b l o o d t r a p p e d w i t h i n the g a s t r o - i n t e s t i n a l t r a c t . matter.  T h i s i s o b v i o u s l y t h e c r u x o f the  I f d e a t h i s due o n l y t o e x s a n g u i n a t i o n i n t o the b o w e l , i t s h o u l d  be p o s s i b l e t o produce d e a t h i n a comparable t i m e and manner b y b l e e d i n g from a n o r m a l dog a volume o f b l o o d e q u a l i n amount t o t h a t t r a p p e d i n the gastro-intestinal tract.  I n 1932, Elman and C o l e made an a t t e m p t t o  measure t h i s amount o f b l o o d . gastro-intestinal tract,  They weighed t h e e v i s c e r a t e d i n t r a - a b d o m i n a l  i n c l u d i n g the s p l e e n and p a n c r e a s ,  following  l i g a t i o n o f t h e p o r t a l v e i n , and compared t h i s w e i g h t w i t h t h e w e i g h t o f e v i s c e r a t e d organs o f n o r m a l dogs o f s i m i l a r w e i g h t and sex i n whom the p o r t a l v e i n had n o t been t i e d .  The i n c r e a s e i n w e i g h t o f t h e organs o f  t h e dog w i t h a l i g a t e d p o r t a l v e i n was assumed t o be due t o t h e passage o f b l o o d i n t o the s p l a n c h n i c v a s c u l a r b e d . was found t o be S.2% o f t h e body w e i g h t .  I n f o u r dogs t h i s  increase  They, t o o , r e c o r d e d t h e  fact  t h a t d e a t h c o u l d be t e m p o r a r i l y p r e v e n t e d b y l i g a t i o n e i t h e r o f t h e  aorta  - 5 above t h e c o e l i a c a x i s o r o f t h e s p l a n c h n i c a r t e r y o r b y b l o o d t r a n s f u s i o n , u s u a l l y 1,000 m l . and more t o m a i n t a i n the b l o o d p r e s s u r e above t h e l e v e l o f 50-60 mm. o f m e r c u r y . gangrene o f t h e g u t .  However, d e a t h was e v e n t u a l l y caused b y  They c o u l d n o t s u b s t a n t i a t e t h e presence o f any t o x i n  i n t h e t h o r a c i c d u c t lymph when i t was i n j e c t e d i n t o g u i n e a p i g s , if,  after  critical  finally,  l i g a t i o n o f t h e p o r t a l v e i n , the i n t e s t i n a l t r a c t was removed,  d e a t h was p o s t p o n e d .  They c o n c l u d e d t h a t the r a p i d death p r o d u c e d b y  l i g a t i o n i s due t o l o s s o f b l o o d  froim  t h e s y s t e m i c i n t o the p o r t a l system, I n 1933,  w h i c h r e d u c e s t h e b l o o d p r e s s u r e below t h a t c o m p a t i b l e w i t h l i f e .  M c M i c h a e l and S m i r k , w o r k i n g w i t h r a t s r e c o r d e d as an i n c i d e n t a l o b s e r v a t i o n t h a t i n two r a t s w i t h complete o b l i t e r a t i o n o f the p o r t a l v e i n ,  the  w e i g h t o f t h e g u t i n c r e a s e d from an average o f 5.5$ o f t h e body w e i g h t t o 11.5$ and 12.5$.  B o t h t h e s e r a t s d i e d i n a few h o u r s .  B u t i n 1935, B o y c e ,  Lampert and M c F e t r i d g e r e p e a t e d t h i s work u s i n g seven d o g s .  Their figure  f o r t h e i n c r e a s e i n w e i g h t o f t h e g u t was 3.05$ o f t h e body w e i g h t . N a t u r a l l y t h e i r c o n c l u s i o n s d i f f e r e d , f o r t h e y were a b l e t o b l e e d a c o n t r o l s e r i e s o f dogs i+-5$ o f t h e i r body w e i g h t w i t h o u t shock o r d e a t h . 5.8$ t h e a n i m a l s d i e d o f s h o c k .  T h e i r t h e o r y was t h a t d e a t h  Beyond  following  l i g a t i o n o f the p o r t a l v e i n was due t o n e u r o g e n i c shock, w h i c h p r o d u c e d the rapid i n i t i a l f a l l ,  and t h e f a l l was m a i n t a i n e d b y t h e l o s s o f b l o o d .  Despite these d i s c r e p a n t f i n d i n g s , probably the r e s u l t of u s i n g s m a l l numbers o f a n i m a l s i n r a t h e r crude e x p e r i m e n t s ,  l i t t l e f u r t h e r was done  u n t i l 1950, when M a l l e t - G u y , D e v i c and Gangolphe r e p e a t e d Elman and C o l e ' s work.  They found t h a t 5.0$ o f the body w e i g h t was t r a p p e d w i t h i n  gastro-intestinal tract.  the  B y u s i n g C h i c a g o - b l u e dye t h e y a l s o measured  the  p r e l i g a t i o n and p o s t l i g a t i o n b l o o d v o l u m e s , and found a decrease o f lu9$  - 6 of the body weight, or h9*3% of the circulating blood volume. 2.  Chronic Obliteration Ore's paper (1856) recorded the fact that dogs survived chronic  obliteration of the portal vein. His method was to place a ligature about the vein bringing the ends out onto the abdominal w a l l , and after an interval, gradually obliterating the vein over a period of days. Examination of his dogs showed that an anastomosis between the great mesenteric vein and the i n f e r i o r vena cava had developed. Claude Bernard recorded a similar experiment, and i n 1875 Solowieff f i r s t demonstrated that dogs could survive occlusion of the portal vein i f the branches were ligated at different times.  He ligated the superior mesenteric vein at the f i r s t  operation, the gastrosplemic vein a few days later and f i n a l l y the portal vein above the gastrosplenic. His dogs survived for some time.  Neuhof  (1913) repeated Solowieff's experiments, and confirmed them, though they had not been confirmed by Ito andOrni i n 1901.  He found, as had the  previous authors, that a well marked c o l l a t e r a l circulation developed. It was to this type of c o l l a t e r a l circulation that Pick (1909) gave the name "hepato-petal".  Neuhof was also able to narrow the lumen of the  portal vein to occlusion by successive operations.  Further confirmation  was provided by Dragstedt (1931), McMichael (1933) and Boyce, Lampert and McFetridge (1935). Boyce noted that two-thirds occlusion of the vein could cause death, and that l i g a t i o n of one branch of the portal vein, when f o l lowed seven days later by l i g a t i o n of the other, was also followed by death.  Time had to be allowed for collaterals to form. Interest again  arose with attempts to produce ascites by experimental subtotal obliteration of the p o r t a l vein. A l l attempts (Kunkel and Eisenmenger (19^9) -  r a t s ; Volwiler e t a l .  (1950); Morris and M i l l e r ( l 9 5 l ) , Laufman et a l  (19^2) - dogs) f a i l e d to produce permanent ascites because of the development of adequate c o l l a t e r a l c i r c u l a t i o n .  In any event, i t has been known  since Eck (1877) f i r s t produced a t o t a l bypass of the p o r t a l venous blood from the l i v e r into the i n f e r i o r vena cava, that such blood was not necessary f o r s u r v i v a l .  3.  Intermittent Occlusion of the P o r t a l Vein Several authors have noted that intermittent complete occlusion  of the p o r t a l vein i s t o l e r a t e d (Mosselman and Lienaux - 1885, et a l , 1950).  Boyce e t a l (1935) quote two Russian papers  Mallet-Guy -  (Roger and  Duchinowa,and TscherndJkoff ) as saying that 35 minutes i s not f a t a l , while Rafucci and Wangensteen (l95l) have recorded that 20 minutes i s the maximum period f o r the occlusion of the t o t a l afferent supply to the liver.  U.  Species Difference The experiments quoted above were performed mainly with the dog,  although some workers used the r a b b i t and the r a t .  In these animals, death  i n e v i t a b l y follows sudden occlusion of the p o r t a l v e i n . l i g a t e d the p o r t a l vein of a pigeon.  Claude Bernard  The b i r d survived the l i g a t i o n , but  died next morning from an unknown cause.  Birds have a vein, a t r i b u t a r y  of the renal vein, which receives blood from the t a i l and lower rectum, and then j o i n s i t s fellow of the opposite side to form a trunk which drains the  blood of the large i n t e s t i n e .  At the upper part of the rectum i t be-  comes continuous with the trunk of the veins draining the small i n t e s t i n e to form the p o r t a l v e i n .  By t h i s large communication i n the p e l v i s  - 8 between p o r t a l and  systemic veins, blood from the v i s c e r a can flow i n d i f -  f e r e n t l y into the vena cava, or into the p o r t a l vein and thence to the l i v e r , (venous system of Jacobson).  Bernard found that l i q u i d injected into the  i n f e r i o r vena cava would not flow into the p o r t a l system, but when injected into the p o r t a l vein, would flow into the vena cava.  He remarked that only  i n mammals does the p o r t a l vein form a closed system communicating with the systemic c i r c u l a t i o n only through the In 19h9  liver.  Milnes and C h i l d showed that sudden, complete  of the p o r t a l vein i n Macacus Rhesus monkeys was  not f a t a l .  so l i g a t e d , a l l survived 16 to $1 days postoperatively.  occlusion  Of 7 monkeys  Portal venography  showed that p e l v i c porto-systemic anastomoses occurred naturally, immediately c a r r i e d much of the blood. unless the l i g a t u r e was  and  Observers had early noted that  placed on the hepatic side of the l a s t p o r t a l vein  t r i b u t a r y , s u r v i v a l could occur (Castaigne and Bender - 1 8 9 1 , Kusnetzow 1900).  Douglass et a l .  (1951)  noted s u r v i v a l of a dog a f t e r l i g a t i o n of  the p o r t a l vein, the l i g a t u r e being on the i n t e s t i n a l side of a small pancreatic vein.  Both Ore and Claude Bernard had noted that  peritoneal  adhesions c a r r i e d p o r t a l systemic anastomoses, and that the p o r t a l v e i n could be l i g a t e d i n such animals.  Brunschwig et a l .  (19U5)  had no success  when attempting t h i s , however, as an experimental method to enable dogs to survive acute l i g a t i o n .  I t would appear that when there i s adequate  c o l l a t e r a l c i r c u l a t i o n , either by naturally occurring  porto-systemic  venous communication, by adhesions, or by malposition of the l i g a t u r e , s u r v i v a l occurs a f t e r p o r t a l vein l i g a t i o n . a f t e r l i g a t i o n of the p o r t a l vein (dog,  In those animals which die  rabbit and r a t ) , there i s no  l i t e r a t u r e concerning the extent of such c o l l a t e r a l c i r c u l a t i o n .  5.  O c c l u s i o n o f t h e P o r t a l V e i n i n Man Neuhof p r o p o s e d , i n 1913, t h e n e c e s s i t y f o r knowing t h e  o f l i g a t i o n o f t h e p o r t a l v e i n i n man. t i m e was s u p p u r a t i v e p y l e p h l e b i t i s .  results  His specific indication at  that  On the b a s i s o f h i s own e x p e r i m e n t a l  w o r k , c a r r i e d o u t i n t h e l a b o r a t o r y o f P r o f e s s o r P i c k i n B e r l i n , and t h e work o f o t h e r s a l r e a d y r e v i e w e d , he r e a l i z e d t h e n e c e s s i t y o f an adequate c o l l a t e r a l c i r c u l a t i o n between t h e p o r t a l and s y s t e m i c v e i n s b e f o r e t i o n c o u l d be c o n s i d e r e d .  He s u g g e s t e d the r e q u i r e m e n t s  liga-  f o r such an  o p e r a t i o n , b u t he d i d n o t seem t o have performed i t on any  patient.  Neuhof r e c o r d s t h e r e p o r t o f 6 c a s e s b y G i n t r a c (1857) where a t p o s t mortem t h e p o r t a l v e i n was found o c c l u d e d , and t h e  anastomotic  c o l l a t e r a l s resembled t h o s e o c c u r r i n g i n c i r r h o s i s o f t h e l i v e r , as d e s c r i b e d b y F r e r i c h s ( l 8 6 l ) , Charpy (1898) and P i c k (1909).  later  He q u o t e s  Brewer as h a v i n g l i g a t e d t h e p o r t a l v e i n as a r e s u l t o f a c c i d e n t a l i n j u r y , b u t B r e w e r ' s p a t i e n t had a c t u a l l y a h y d a t i d c y s t w h i c h had so r e d u c e d c a l i b r e o f the p o r t a l v e i n w h i c h was s t r e t c h e d o v e r i t as t o a l l o w f o r m a t i o n o f adequate c o l l a t e r a l s . patient.  the  the  The l i g a t i o n had no e f f e c t on the  I n 1926 C o l p r e p o r t e d t h e r e s u l t s o f l i g a t i o n i n t h r e e  w i t h p y l e p h l e b i t i s , a l l o f whom e v e n t u a l l y d i e d .  patients  The f i r s t case, r e p o r t e d  i n 1915 b y Beer, had an omentopexy t h r e e days p r i o r t o l i g a t i o n o f t h e portal vein.  The l i g a t i o n had no e f f e c t on the p u l s e r a t e and a t  autopsy  f o u r days l a t e r t h e r e was e v i d e n c e o f a w e l l formed c o l l a t e r a l c i r c u l a t i o n . I n the second c a s e ,  l i g a t u r e f o l l o w e d 36 hours a f t e r p a r t i a l o c c l u s i o n .  Death o c c u r r e d seven days l a t e r ,  and t h e a u t o p s y showed thrombus w i t h i n the  p o r t a l v e i n , w i t h no e v i d e n c e o f c o l l a t e r a l c i r c u l a t i o n b u t w i t h o u t o f t h e v e s s e l s l e a d i n g t o the p o r t a l v e i n .  I n the l a s t c a s e ,  death  stasis  - 10 -  o c c u r r e d three hours a f t e r  l i g a t i o n o f the p o r t a l v e i n which contained  f l u i d b l o o d , b u t t h e r e was no a u t o p s y r e p o r t .  I n 19kh B r u n s c h w i g , i n  t h e c o u r s e o f e x t e n s i v e r e s e c t i o n s f o r c a r c i n o m a o f the p a n c r e a s ,  divided  the p o r t a l v e i n a c c i d e n t a l l y .  I n 1°U5  a further  The p a t i e n t d i e d a f t e r  two h o u r s .  c a s e o f B r u n s c h w i g e t a l . a r o s e i n w h i c h the p o r t a l v e i n was  t i e d w i t h o u t d e a t h o c c u r r i n g , b u t a p r e v i o u s p e l v i c o p e r a t i o n had produced p o r t o - s y s t e m i c anastomoses.  I n 1952, as a r e s u l t o f t h e i r work on the  Macaca M u l a t t a monkey, C h i l d e t a l . d e c i d e d t o l i g a t e the p o r t a l v e i n deliberately i n patients,  as a t w o - s t a g e p r o c e d u r e d u r i n g o p e r a t i o n s o f  r a d i c a l p a n c r e a t i c o d u o d e n e c t o m y where t h e p o r t a l v e i n had been i n v a d e d b y neoplasm.  They had a l r e a d y t r i e d t o p e r f o r m a r a d i c a l p a n c r e a t i c o -  duodenectomy t o g e t h e r w i t h l i g a t i o n and e x c i s i o n o f a p o r t i o n o f t h e p o r t a l v e i n , b u t had f a i l e d due t o t h e massive haemorrhage w h i c h o c c u r r e d from the b e d o f t h e p a n c r e a s .  F o r t h i s reason they planned to a l l o w time  for a c o l l a t e r a l c i r c u l a t i o n to enlarge. on two p a t i e n t s ,  The o p e r a t i o n s were p e r f o r m e d  w i t h o u t death o c c u r r i n g a f t e r the f i r s t stage l i g a t i o n .  I n t h e f i r s t c a s e , p r e v i o u s p o r t a l venography showed t h a t t h e r e d i d n o t seem t o be any o b s t r u c t i o n t o t h e p o r t a l v e i n , though t h e neoplasm was i n c l o s e r e l a t i o n , b u t i n t h e second t h e r e was a n g u l a t i o n o f the v e i n b y the growth.  The e x i s t e n c e o f c o l l a t e r a l s was n o t commented u p o n .  o p e r a t i v e p o r t a l venogram showed w e l l marked p e l v i c  I n an e a r l i e r - r e p o r t  A post-  anastomoses.  (1952) C h i l d e t a l . r e c o r d t h a t t h e y had  l i g a t e d the p o r t a l v e i n i n a s i n g l e s t a g e i n f i v e p a t i e n t s who had c a r cinoma o f t h e stomach o r head o f t h e p a n c r e a s . g r a p h i c e v i d e n c e s o f o b s t r u c t i o n , f o u r had n o t .  None d i e d .  One had v e n o -  They f u r t h e r  quote  B a r c l a y ( l ? 5 l ) and P e r s o n (1951) as h a v i n g r e s e c t e d t h e p o r t a l v e i n ,  but  - 11 i n b o t h t h e s e c a s e s t h e i m p r e s s i o n was t h a t t h e r e was p a r t i a l o c c l u s i o n from the n e o p l a s m .  These c l i n i c a l e x p e r i e n c e s w o u l d seem t o show t h a t  a c u t e l i g a t i o n o f t h e p o r t a l v e i n i s n o t l e t h a l i n man, though i n a l l the c a s e s r e p o r t e d t h e r e i s no c l e a r e v i d e n c e o f l a c k o f p r e v i o u s t o the p o r t a l v e i n .  Such o b s t r u c t i o n ,  development o f p o r t o - s y s t e m i c  6.  obstruction  i f p r e s e n t , might have caused  the  anastomoses.  L i g a t i o n of a Main Branch o f the P o r t a l V e i n Mclndoe and C o u n s e l l o r (1927) b y i n j e c t i o n o f t h e main r i g h t  and l e f t b r a n c h e s o f t h e p o r t a l v e i n , h e p a t i c a r t e r y and h e p a t i c  duct,  showed t h a t t h e main p l a n e o f d i v i s i o n between r i g h t and l e f t l o b e o f t h e l i v e r l i e s between the f o s s a o f t h e g a l l b l a d d e r and t h e  inferior  vena c a v a a t the e n t r a n c e o f the h e p a t i c v e i n s , t h u s c o n f i r m i n g p r e v i o u s i n v e s t i g a t i o n ( C a n t l i e - 1898, Serege - 1901).  F u r t h e r , t h e r e was no  communication between t h e r i g h t and l e f t b r a n c h e s a c r o s s t h i s p l a n e i n the l i v e r .  These o b s e r v a t i o n s  and b y a u t o p s y m a t e r i a l .  have been borne o u t b y e x p e r i m e n t a l work  Injections  i n t o e i t h e r o f t h e p o r t a l venous  branches are d i s t r i b u t e d o n l y to the i p s i l a t e r a l lobe ( B a r t l e t t et a l . 19lU, Copher and D i c k - 1928).  I f a main b r a n c h o f t h e p o r t a l v e i n i s  l i g a t e d , t h e i p s i l a t e r a l l o b e w i l l a t r o p h y (Rous - 1920, L o e f f l e r G r i n d l a y and B o l l m a n - 1952).  -  A u t o p s y m a t e r i a l has shown t h a t  - 1936,  obstruction  o f a main b r a n c h o f t h e p o r t a l v e i n has r e s u l t e d i n a t r o p h y o f the  lobe  o f t h a t s i d e ( C a n t l i e - I898, R o l l e s t o n and McNee - 1929, Benz e t a l 1952).  T h i s d i v i s i o n i n t o two l o b e s has f u n c t i o n a l s i g n i f i c a n c e as w e l l .  O l i v e o i l i n j e c t e d i n t o the stomach, s p l e e n , duodenum, upper jejunum and rectum p a s s e s t o the l e f t and c e n t r a l p o r t i o n o f t h e l i v e r and when i n j e c t e d i n t o t h e l o w e r jejunum, i l e u m and p r o x i m a l t h r e e - q u a r t e r s o f  the  -  large intestine,  12 -  i t p a s s e s t o the r i g h t l o b e ( B a r t l e t t e t a l . -  19ll|).  Copher and D i c k (1928) were a b l e t o watch t h i s s t r e a m l i n i n g e f f e c t  directly  b y i n j e c t i n g t r y p a n b l u e i n t o t h e o r g a n s , and t r a n s i l l u m i n a t i n g t h e vein.  portal  T h e i r work was c o n f i r m e d b y Hahn e t a l . (19U5), who u s e d r a d i o -  a c t i v e phosphorus.  D a n i e l and P r i c h a r d (195l) were u n a b l e t o c o n f i r m t h i s  i n l a b o r a t o r y animals b y i n j e c t i o n i n t o a branch o f the s u p e r i o r  mesenteric  v e i n , f o r the T h o r o t r a s t t h e y u s e d p e r f u s e d the whole l i v e r , and s i m i l a r f i n d i n g s were r e c o r d e d b y D r e y e r and B u d t z - O l s e n (1952) when t h e y c a r r i e d o u t p e r c u t a n e o u s s p l e n i c venography w i t h 70% d i o d o n e .  I t has a l s o been  w e l l known t h a t a n i m a l s w i t h a n Eck f i s t u l a f a i l t o r e g e n e r a t e liver  ( G r i n d l a y and B o l l m a n - 1952, Mann and Magath - 1922).  ablated Therefore,  though o c c l u s i o n o f a b r a n c h o f t h e p o r t a l v e i n i s n o t f a t a l , t h e  portal  venous b l o o d i s n e c e s s a r y f o r the p r o p e r n u t r i t i o n o f the i p s i l a t e r a l l o b e , the h e p a t i c a r t e r y b y i t s e l f b e i n g i n s u f f i c i e n t .  Deprivation of  the t o t a l p o r t a l venous b l o o d s u p p l y i s n o t f o l l o w e d b y a t r o p h y , regeneration  i s impossible.  but  B u r n e t t e t a l . (1951) has shown i n r a t s  d e p r i v a t i o n o f p o r t a l venous b l o o d r e s u l t s  i n f a i l u r e of the l i v e r  to  d e v e l o p , whereas i n c r e a s i n g t h e amount o f p o r t a l venous b l o o d r e s u l t s an i n c r e a s e d r a t e o f l i v e r development.  C h i l d e t a l . (1953) c a r r i e d  so t h a t a l l p o r t a l b l o o d was  d i v e r t e d from the l i v e r d i r e c t l y i n t o t h e i n f e r i o r vena c a v a ; t h e h e p a t i c p o r t a l b e d was f i l l e d w i t h s y s t e m i c venous b l o o d . one month l a t e r ,  in  However, i t i s n o t p o r t a l venous  blood which i s e s s e n t i a l f o r regeneration. out, i n dogs, p o r t o c a v a l t r a n s p o s i t i o n ,  that  p a r t i a l hepat:ec tomy was c a r r i e d o u t .  intra-  Approximately  I n n o r m a l dogs,  t h e l i v e r r e g e n e r a t e d t o 7S% o f the w e i g h t o f the e x c i s e d p o r t i o n ; i n t h o s e w i t h p o r t o c a v a l t r a n s p o s i t i o n , t h e r e g e n e r a t i o n was $0%.  The  -  13  -  s u b s t i t u t i o n o f s y s t e m i c venous b l o o d f o r p o r t a l venous b l o o d s t i l l a l l o w s adequate r e g e n e r a t i o n .  There does n o t appear t o be any f a c t o r p e c u l i a r  p o r t a l venous b l o o d w h i c h i s n e c e s s a r y f o r l i v e r r e g e n e r a t i o n . ference  to  The d i f -  i n amount r e g e n e r a t e d i s p r o b a b l y t o be a t t r i b u t e d t o the  lesser  f l o w o f b l o o d i n t h e i n f e r i o r vena c a v a b e l o w t h e h e p a t i c v e i n s , when compared w i t h t h e p o r t a l venous  7.  flow.  L i g a t i o n o f the H e p a t i c V e i n s . Whereas l i g a t i o n o f the p o r t a l v e i n i s r e l a t i v e l y e a s y ,  tributaries  a l l its  e v e n t u a l l y forming a s i n g l e v e s s e l w e l l p l a c e d f o r a l i g a t u r e ,  l i g a t i o n o f t h e h e p a t i c v e i n s i s most d i f f i c u l t .  Simonds and Brandes  (192$) f i r s t d e s c r i b e d a method o f o c c l u d i n g the h e p a t i c v e i n s w i t h o u t o c c l u d i n g the i n f e r i o r vena c a v a . t u b e , 0 . 5 cm. i n d i a m e t e r ,  They u s e d dogs, and p a s s e d a r u b b e r  2 f e e t l o n g around t h e l i v e r i n such a way t h a t  t r a c t i o n on t h e ends o f t h e lbube, w i t h c o u n t e r t r a c t i o n on t h e would produce o c c l u s i o n o f the h e p a t i c v e i n s o n l y . duced a p r e c i p i t a t e  Such o c c l u s i o n p r o -  f a l l i n b l o o d p r e s s u r e , and e l e v a t i o n o f p r e s s u r e  w i t h i n the p o r t a l v e i n . the i n t e s t i n e s  liver,  Engorgement o f t h e l i v e r was marked, t h a t o f  n o t so marked.  o f flow i n the hepatic a r t e r y .  The l i v e r engorgement p r o d u c e d a c e s s a t i o n Once t h e p r e s s u r e f a l l had s t a b i l i z e d , i f  the c o n s t r i c t i o n was m a i n t a i n e d , no f u r t h e r  f a l l occurred.  I t has been  shown, however, t h a t i t i s r e a l l y v e r y h a r d even i n t h i s way t o e n s u r e complete o c c l u s i o n o f t h e h e p a t i c v e i n s . p r o b l e m as an e x p l a n a t i o n o f t h e e f f e c t  Simonds was i n t e r e s t e d  i n the  o f peptone " s h o c k " i n d o g s .  He  and A r e y (1920) had a l r e a d y c a l l e d a t t e n t i o n t o the l a r g e amount o f p l a i n muscle i n t h e w a l l s o f t h e h e p a t i c v e i n s o f the dog and  suggested  t h a t s u c h m u s c l e , thrown i n t o spasm upon the i n t r o d u c t i o n o f the  protein  - U* t o w h i c h the a n i m a l had been s e n s i t i z e d , r e s t r i c t e d the f l o w t h r o u g h the liver.  It is difficult  t o c o r r e l a t e these f i n d i n g s w i t h those o f acute  l i g a t i o n o f t h e p o r t a l v e i n , f o r i t i s n o t p o s s i b l e t o determine whether t h e h e p a t i c v e i n s were c o m p l e t e l y l i g a t e d , i n t h e e x p e r i m e n t s c i t e d . Armstrong and R i c h a r d s  (I9kk)  succeeded i n a c h r o n i c l i g a t i o n  o f the h e p a t i c v e i n s i n t h r e e dogs w i t h s i m i l a r r e s u l t s . u s i n g c a t s and monkeys, n o t e d t h a t complete l i g a t i o n , fifths  or more t h a n  three-  o c c l u s i o n o f the i n f e r i o r vena cava above t h e h e p a t i c v e i n s  r e s u l t e d i n d e a t h w i t h i n a few h o u r s . fifths  B o l t o n (19LU),  and t h r e e - f i f t h s  When t h e o c c l u s i o n was between t w o -  o f the c a l i b f e o f t h e v e i n a s c i t e s appeared w h i c h  o n l y l a s t e d f o r two t o t h r e e months, u n t i l adequate c o l l a t e r a l s d e v e l o p e d .  Subsequent i n v e s t i g a t o r s have a l s o been c o n t e n t t o l i g a t e the i n f e r i o r v e n a c a v a a t t h e diaphragm ( K i r s c h n e r e t a l . - 19^5, Laufman e t a l . 1951, Berman and H u l l -  1952,  Milnes -  1952,  Jefferson et a l . -  1953).  A l l have n o t i c e d t h a t a s c i t e s appeared i n a few days and d i s a p p e a r e d w i t h i n a few months.  Kirschner et a l .  (19U5)  n o t e d , as a major c o l l a t e r a l t r u n k ,  the presence o f a l a r g e d i a p h r a g m a t i c v e i n w h i c h j o i n s a l e f t h e p a t i c v e i n j u s t before i t s e n t r y i n t o the i n f e r i o r vena c a v a .  8.  Hepatic A r t e r y L i g a t i o n The r e s u l t o f l i g a t i o n o f t h e h e p a t i c a r t e r y has been a c o n t e n -  t i o u s s u b j e c t f o r many y e a r s .  When t h e dog was u s e d as t h e e x p e r i m e n t a l  a n i m a l , i t was r e a l i z e d as l o n g ago as 1898 (Doyon and D u f o u r t ) t h a t s u r v i v a l was t h e r u l e i f adequate c o l l a t e r a l c i r c u l a t i o n remained from t h e o t h e r b r a n c h e s o f t h e c o e l i a c a x i s , and t h i s was c o n f i r m e d as  the  - 1$ -  y e a r s went b y (Haberer - 1905, S e g a l l - 1923).  I t i s not s u f f i c i e n t  to  l i g a t e t h e h e p a t i c a r t e r y j u s t b e f o r e i t s d i v i s i o n s , f o r branches may j o i n d i s t a l to t h i s .  The p h r e n i c v e s s e l s c o n t r i b u t e b r a n c h e s between  c a p s u l e and n e i g h b o r i n g v e s s e l s ,  and f u r t h e r v e s s e l s r u n a l o n g the  the  liga-  mentum venosum, and a l o n g p o r t a l v e i n , vena c a v a , and common b i l e d u c t ( J e f f e r s o n e t a l . - 1952).  F u r t h e r , b r a n c h e s may a r i s e e a r l y , and p a s s  t o t h e l o b e , t h u s b y p a s s i n g t h e s i t e o f the l i g a t u r e .  I t i s the absence  o f such w e l l marked c o l l a t e r a l c i r c u l a t i o n i n t h e r a b b i t and g u i n e a p i g w h i c h l e a d s t o t h e i r d e a t h when a c e n t r a l b r a n c h i s l i g a t e d .  The c a t  behaves i n the same manner as t h e dog (Behrend e t a l . - 1922).  I n man,  the r e s u l t s o f l i g a t i o n a r e b a s e d on c l i d c a l o b s e r v a t i o n s i n c a s e s h a v i n g e i t h e r a c c i d e n t a l l i g a t i o n or thrombosis of the a r t e r y .  In a review of  28 c a s e s t o 1932, Graham and C a n n e l l c o n f i r m e d an o b s e r v a t i o n o f R i t t e r t h a t the hepatic a r t e r y t r u n k ,  o r t h e a r t e r y p r o p e r , b e f o r e the  g a s t r i c a r t e r y i s g i v e n o f f , can be l i g a t e d w i t h o u t n e c r o s i s  right  ensuing.  Where the l i g a t i o n t a k e s p l a c e beyond t h i s p o i n t , n e c r o s i s ensues, i f t h e a r t e r y was p r e v i o u s l y h e a l t h y (Graham and C a n n e l l - 1932, Zimmerman - 1930). However, so f a r , no b a c t e r i o l o g i c a l s t u d y has been made i n s u c h c a s e s ,  for  i t s i m p o r t a n c e , as w i l l be s e e n , has o n l y l a t e l y been r e c o g n i z e d .  I n t h e Macaca M u l a t t a monkey, C h i l d e t a l . (1952) found t h a t l i g a t i o n o f t h e h e p a t i c a r t e r y was not n e c e s s a r i l y f o l l o w e d b y d e a t h . By c a r e f u l r e s e c t i o n o f a l l branches  o f the h e p a t i c a r t e r y from i t s  a t the c o e l i a c a x i s t o i t s d i s a p p e a r a n c e  i n t o the l i v e r ,  and b y c h e c k i n g  the e f f i c a c y o f t h e r e s e c t i o n b y d i o d r a s t and I n d i a i n k i n j e c t i o n s the a o r t a ,  origin  into  i t was t h o u g h t t h a t t h e s o u r c e o f a l l h e p a t i c a r t e r i a l b l o o d  was removed.  B u t others have p o i n t e d o u t t h a t i n dogs the o n l y c e r t a i n  - 16 e v i d e n c e o f t h e absence o f a r t e r i a l b l o o d , i s t h e c a r e f u l postmortem d i s section of a l l vessels,  t h e a o r t a h a v i n g been i n j e c t e d t o d i s p l a y any c o l -  l a t e r a l s however f i l a m e n t o u s . 1952).  ( J e f f e r s o n e t a l . - 1902, Popper e t a l . -  P r e v i o u s d i s c r e p a n c i e s i n r e s u l t s o f l i g a t i o n were due t o f a i l u r e  t o observe t h i s c r i t e r i o n . I t was a n a c c i d e n t a l o b s e r v a t i o n o f M a r k o w i t z , Rappaport and S c o t t (19U9) w h i c h f u r n i s h e d a c l u e t o t h e cause o f d e a t h .  During attempts  to a r t e r i a l i z e the p o r t a l v e i n , b y using a s p l e n i c a r t e r y t o splenic v e i n anastomosis, technique.  p e n i c i l l i n was e x h i b i t e d t o c o v e r any b r e a k s i n t h e a s e p t i c A t t h e c o n c l u s i o n o f t h e o p e r a t i o n t h e h e p a t i c a r t e r y was l i g a t e d  as c o m p l e t e l y as p o s s i b l e .  The dog s u r v i v e d , b u t a t postmortem e x a m i n a t i o n  l a t e r t h e anastomosis was found t o b e thrombosed.  Thus p e n i c i l l i n seemed t o  have had t h e power o f i n h i b i t i n g t h e f a t a l e f f e c t o f h e p a t i c a r t e r y l i g a t i o n . T h e i r work has been c o n f i r m e d many t i m e s ( D a v i s e t a l . - 19^9, T a n t u r i e t a l . - 1950, Chau e t a l . - 195l).  The e x p l a n a t i o n o f f e r e d i s t h a t t h e a n t i -  b i o t i c i n h i b i t s t h e growth o f anaerobes and t h e p r o d u c t i o n b y them o f l e t h a l enzymes such as l e c i t h i n a s e , u n t i l t h e development o f a n adequate c o l l a t e r a l a r t e r i a l s u p p l y ( M a r k o w i t z and Rappaport - 195l, T a n t u r i e t a l . 19^0).  I f s u c h a n a r t e r i a l c o l l a t e r a l s u p p l y does n o t d e v e l o p , t h e a n i m a l  w i l l d i e d e s p i t e a n t i b i o t i c s (Popper - 1952). does n o t a c c o u n t f o r a l l t h e f a c t o r s fact,  involved.  B u t such an e x p l a n a t i o n This i n v e s t i g a t i o n , i n  had i t s f i r s t b e g i n n i n g s i n some i n v e s t i g a t i o n s t h a t J a c k s o n had been  making i n t o t h e e f f e c t  o f v a r i o u s c o n d i t i o n s on t h e l a t e n t p e r i o d and  r a t e o f a s e p t i c postmortem a u t o l y s i s  ( J a c k s o n - 1909)•  He asked Wolbach  and S a i k i i n t h e same y e a r t o i n v e s t i g a t e a b a c i l l u s w i t h p e c u l i a r m o r p h o l o g i c a l and c u l t u r a l c h a r a c t e r i s t i c s w h i c h he h a d found i n t h e l i v e r .  - 17 They u s e d 23 d o g s , k i l l e d them, b u r n t t h e a b d o m i n a l w a l l , and removed the greater p o r t i o n o f the l i v e r .  The p i e c e s were i n c u b a t e d a e r o b i c a l l y and  a n a e r o b i c a l l y , and i n 21 dogs under a n a e r o b i c c o n d i t i o n s , t h e r e were marked changes a f t e r  18 t o 2h h o u r s .  much gas p r o d u c t i o n .  The l i v e r was s o f t ,  g r e e n and r a n c i d , w i t h  C o n t r o l c u l t u r e s o f t h e s p l e e n and k i d n e y f a i l e d ,  ( e x c e p t i n one c a s e ) t o produce the same o r g a n i s m s . s p o r e - b e a r i n g , n o n - m o t i l e , gram p o s i t i v e .  The b a c i l l u s was 8-9/u.  The f i l t r a t e f r o m t h e  liver  c u l t u r e s had no e f f e c t on i n t r a p e r i t o n e a l i n o c u l a t i o n o f g u i n e a p i g s o r other dogs.  Two l i v e r s were s t e r i l e .  T h i s o r g a n i s m was c o n s i d e r e d t o be  a d e f i n i t e s p e c i f i c b a c i l l u s of dog's l i v e r .  There t h e m a t t e r r e s t e d  16 y e a r s u n t i l Mann (1925) showed t h a t a p i e c e o f l i v e r  (0.5 gms. p e r  for kilo  o f body w e i g h t ) d e t a c h e d and l e f t f r e e i n the p e r i t o n e a l c a v i t y , produced d e a t h from p e r i t o n i t i s i n 18 t o 30 h o u r s .  E l l i s and D r a g s t e d t (1930) b y  a u t o e l a v i n g t h e p i e c e o f l i v e r and t h e n p l a c i n g i t i n the p e r i t o n e a l c a v i t y , f a i l e d t o produce d e a t h .  They a l s o showed t h a t l i v e r o b t a i n e d b y  C a e s a r i a n s e c t i o n from a dog f o e t u s was i n n o c u o u s .  However, the work was  repeated by v a r i o u s others,  and t h e r e s u l t s c e a s e d t o be as  T r u s l e r , M a r t i n and Reeves  (193k, 1935, 1937) i n v e s t i g a t e d  clear-cut. the problem.  They f i r s t p o i n t e d out t h a t t h e o r g a n i s m i n the d o g ' s l i v e r was n o t C I . W e l c h i i o f t o x i c s t r a i n , b u t a s t r i c t anaerobe,  t h e r m o p h i l i c and o f t h e  nonsucrose f e r m e n t i n g , p u t r e f a c t i v e g a s - f o r m i n g t y p e o f t h e genus C l o s tridium.  T h i s same o r g a n i s m was p r e s e n t i n t h e muscle o f d o g s , and i t  f a i l e d t o produce an e x o t o x i n . any s i g n i f i c a n c e i n d i s e a s e .  As a r e s u l t t h e y wondered whether i t had I f o v e r 30 grams o f l i v e r was i m p l a n t e d ,  a l l dogs d i e d (though t h i s was n e a r l y 6 t i m e s g r e a t e r Mann found n e c e s s a r y t o cause d e a t h ) .  t h a n t h e amount t h a t  I n t h i s case t h e r e was a p i c t u r e o f shock  - 18 and the dog l i v e r anaerobe c o u l d be found i n t h e p e r i t o n e a l c a v i t y .  By  s e p a r a t i n g t h e parenchymal elements from the l i v e r c o n n e c t i v e t i s s u e ,  bile  d u c t s and b l o o d v e s s e l s , t h e y found t h a t i m p l a n t a t i o n o f t h e l a t t e r  elements  was a s s o c i a t e d w i t h t h e p i c t u r e o f shock and p e r i t o n i t i s .  they  Further,  f o u n d t h a t i f t h e l i v e r was i n c u b a t e d and t h e n s t e r i l i z e d b y h e a t , o c c u r r e d p r o m p t l y , b u t was n o t due t o b a c t e r i a .  death  They a l s o showed t h a t  b i l e s a l t s cause i n t e n s e i r r i t a t i o n o f the p e r i t o n e a l s u r f a c e s w i t h the p r o d u c t i o n o f severe s h o c k .  l i g a t i o n o f the h e p a t i c a r t e r y w i l l  pro-  duce n e c r o s i s o f the g a l l b l a d d e r and a l l o w the escape o f b i l e i n t o t h e peritoneal cavity.  Mason and D a v i d s o n (l°2i|-25) c o n f i r m e d the presence o f a t o x i c substance  i n the s a l i n e e x t r a c t o f a u t o l y z e d l i v e r , b u t d i d n o t make any  comment about i t s r e l a t i o n t o a b a c t e r i o l o g i c a l o r i g i n .  Andrews and  H r d i n a (1931) because t h e y found t h a t a u t o c l a v e d l i v e r p r o d u c e d the same p i c t u r e - p e r i t o n e a l haemorrhage and e x u d a t i o n , w i t h overwhelming i n f e c t i o n from a gas b a c i l l u s - c o n s i d e r e d t h a t t h e r e a c t i o n was p r o v o k e d b y the sterile material.  Dvorak (1932) found t h a t ground l i v e r always k i l l e d ,  b u t s t e r i l e l i v e r n e v e r d i d so; a kO m l s u s p e n s i o n o f anaerobes was n e c e s s a r y t o k i l l on i n t r a p e r i t o n e a l i n j e c t i o n , and p e r i t o n e a l  fluid  f i l t r a t e s f a i l e d t o k i l l p r o b a b l y because o f a b s o r p t i o n o f t o x i n s b y the host.  B i l e s a l t s were n o t p r e s e n t i n t h e n o r m a l l i v e r o f a dog i n s u f -  f i c i e n t q u a n t i t y t o cause d e a t h .  From t h i s , he c o n c l u d e d t h a t no t o x i n  p r o d u c e d i n t h e l i v e r was r e s p o n s i b l e f o r d e a t h , b u t t h a t b a c t e r i a o r t h e i r t o x i n s were t h e c a u s e .  anaerobic  Boyce and M c F e t r i d g e (1937)  r e p e a t e d many o f t h e s e e x p e r i m e n t s , w i t h o u t however g i v i n g c l e a r o f t h e i r e x p e r i m e n t a l methods.  accounts  A s t h e y seemed t o be a b l e t o produce  - 19 -  d e a t h w i t h s t e r i l e a u t o c l a v e d l i v e r and w i t h f o e t a l l i v e r i n adequate amounts and c o u l d n o t cause d e a t h b y t h e i n t r a p e r i t o n e a l o r i n t r a v e n o u s i n j e c t i o n o f t h e whole p e r i t o n e a l exudate o f a dog dead from a u t o l y t i c p e r i t o n i t i s , t h e y d e c i d e d t h a t t h e r o l e o f t h e gas b a c i l l u s was e n t i r e l y secondary. Chau e t a l . ( I 9 5 l ) found t h a t a l l dogs i n whom the  hepatic  a r t e r y had been c o m p l e t e l y l i g a t e d , d i e d , and a l l had p o s i t i v e b l o o d c u l t u r e s o f C l o s t r i d i a w i t h i n 2 t o 3 hours a f t e r remained p o s i t i v e u n t i l death.  ligation.  S u c c i n y l s u l p h a t h i a z o l e had no e f f e c t  on s u r v i v a l , though C l o s t r i d i a d i s a p p e a r e d from t h e s t o o l s . p e n i c i l l i n had no e f f e c t , effective,  The c u l t u r e s  Pre-operative  b u t p e n i c i l l i n one hour p o s t o p e r a t i v e was  and the b l o o d c u l t u r e r e m a i n e d n e g a t i v e .  f o u n d when aureomycin was u s e d i n s t e a d o f p e n i c i l l i n .  S i m i l a r r e s u l t s were Eze (1952) a l s o  f o u n d t h a t a s i n g l e dose o f p o t a s s i u m p e n i c i l l i n G s u b c u t a n e o u s l y immediately after  o p e r a t i o n p r o t e c t e d the dogs.  N e l s o n (195l) showed t h a t  i n t r a v e n o u s i n f u s i o n s o f pure c u l t u r e s o f p a r a c o l o n b a c i l l i c a n produce r a p i d d e a t h i n dogs i n 2 t o 3 hours w i t h a p i c t u r e o f m e t a b o l i c a c i d o s i s . Thus, t h e r e a r e two w e l l d i v i d e d o p i n i o n s , those who f e e l t h e cause o f d e a t h i s due t o a n a e r o b i c organisms and t h e i r t o x i n s and t h o s e who b e l i e v e the l i v e r , when a u t o l y s e d , produces t o x i n s w h i c h a r e l e t h a l .  Human l i v e r  i s g e n e r a l l y c o n s i d e r e d t o b e s t e r i l e (LewisandWangensteen - 1950, Romieu and B r u n s c h w i g - 1951, Sborov e t a l . - 1952).  PURPOSE OF INVESTIGATION T h i s r e v i e w o f the l i t e r a t u r e r e v e a l s t h a t w h i l e t h e r e i s no disagreement t h a t t h e r e s u l t o f sudden a c u t e l i g a t i o n o f the p o r t a l v e i n i n dogs i s i n e v i t a b l y d e a t h ,  t h e r e i s disagreement about t h e cause o f  - 20 death.  I t i s n o t c e r t a i n l y known what e f f e c t s  or even i n o t h e r a n i m a l s . effects  a c u t e l i g a t i o n has i n man,  T h i s l a c k o f agreement extends a l s o t o  the  o f a c u t e l i g a t i o n o f the h e p a t i c a r t e r y and t h e h e p a t i c v e i n s . The e f f e c t s  o f a c u t e l i g a t i o n o f the p o r t a l v e i n i n man a r e  still  b a s e d on the r e s u l t s o f a n i m a l e x p e r i m e n t a t i o n , b u t t h i s i s s h i f t i n g s a n d , if  even t h e s e r e s u l t s a r e u n c e r t a i n .  Before a b l a t i v e operations are  under-  t a k e n , more c e r t a i n i n f o r m a t i o n must be o b t a i n e d , and i t i s t h e purpose o f t h e s e i n v e s t i g a t i o n s t o employ r e c e n t t e c h n i c a l advances i n a r e s e a r c h o f t h e p r o b l e m as i t a f f e c t s  the d o g .  PLAN OF EXPERIMENTS F o l l o w i n g a c u t e l i g a t i o n o f t h e p o r t a l v e i n , the l e n g t h o f s u r v i v a l was measured, w i t h and w i t h o u t o b l i t e r a t i o n o f the major t e m i c anastomoses.  The p o s i t i o n o f t h e s e anastomoses was i n v e s t i g a t e d .  The r e d u c t i o n i n c i r c u l a t i n g b l o o d volume was measured and t h e o f t h e method employed was examined. v a s c u l a r b e d was measured. been i n d i c a t e d .  porto-sys-  validity  The n o r m a l c a p a c i t y o f t h e  splanchnic  F u r t h e r i n v e s t i g a t i o n s w h i c h are r e q u i r e d have  The methods employed a r e d e t a i l e d under t h e  " E x p e r i m e n t a l " and the r e s u l t s o b t a i n e d a r e r e c o r d e d under  heading  "Observations".  A s p e c i f i c d i s c u s s i o n f o l l o w s each s e t o f o b s e r v a t i o n s , t h e g e n e r a l d i s c u s s i o n b e i n g employed f o r more g e n e r a l s p e c u l a t i o n .  EXPERIMENTAL EXPERIMENTAL METHOD 1.  General Pound dogs were u s e d , u n s e l e c t e d as t o w e i g h t , s e x or g e n e r a l  condition.  They were s t a r v e d o v e r n i g h t , b u t were w i t h o u t w a t e r  restrictions.  P r i o r to being anaesthetized,  t h e y were encouraged t o empty t h e i r  b l a d d e r s , and were t h e n w e i g h e d .  A n a e s t h e s i a was produced b y the  venous i n j e c t i o n i n t o a forepaw v e i n o f sodium p e n t o b a r b i t a l , 30 mgm/kg body w e i g h t .  intra-  using  The dogs were i n t u b a t e d w i t h an e n d o t r a c h e a l  t u b e and p l a c e d on a warmed o p e r a t i n g t a b l e .  The abdomen was opened b y  a m i d l i n e i n c i s i o n , c a r e b e i n g t a k e n t o reduce b l e e d i n g t o a minimum; (by m e a s u r i n g the i n c r e a s e i n w e i g h t o f d r y gauze sponges u s e d f o r mopping, b l o o d l o s s d i d n o t exceed 10 t o 20 m l . ) .  D u r i n g the p e r i o d between  m a n i p u l a t i o n s , the abdominal w a l l was c l o s e d i f i t was p o s s i b l e t o do s o , u s u a l l y by A l l i s t i s s u e forcepsj t o w e l s soaked i n s a l i n e .  i f i m p o s s i b l e , the wound was p r o t e c t e d b y  The l e n g t h o f any e x p e r i m e n t seldom exceeded  2 h o u r s , and i t was u s u a l l y u n n e c e s s a r y t o g i v e a f u r t h e r dose o f sodium pentobarbital. experiment. tube.  The a n i m a l s were u n c o n s c i o u s d u r i n g t h e whole o f t h e  They r e c e i v e d no i n t r a v e n o u s t h e r a p y n o r f l u i d b y oesophageal  The t e m p e r a t u r e w i t h i n the o p e r a t i n g room was f a i r l y c o n s t a n t  7 0 ° and 7 5 ° F .  between  The i n s t a n t o f d e a t h was t a k e n as t h e l a s t c o n t r a c t i o n o f  t h e l e f t v e n t r i c l e o f t h e h e a r t s u f f i c i e n t t o be r e c o r d e d b y a mercury b l o o d p r e s s u r e manometer.  T h i s p o i n t was u s u a l l y preceded by s e v e r a l  c o n v u l s i v e r e s p i r a t o r y movements.  2.  Blood  Pressure A c o n t i n u o u s r e c o r d o f the b l o o d p r e s s u r e was o b t a i n e d b y a  mercury manometer.  The l e f t common c a r o t i d a r t e r y was exposed b y d i s -  s e c t i o n , l i g a t e d d i s t a l l y , and the p r o x i m a l p o r t i o n c a n n u l a t e d w i t h a N o . 12 b l u n t - e n d e d c a n n u l a w h i c h was t i e d i n .  The c a n n u l a and t u b i n g were  f i l l e d w i t h 3 . 6 $ sodium c i t r a t e s o l u t i o n .  The t u b i n g was v i n y l p l a s t i c  which r e s i s t s l a t e r a l expansion of i t s w a l l s ( A r s t et a l . - 1951).  - 22 3.  B l o o d Samples These were o b t a i n e d u s i n g d r y , s i l i c o n e d , a l l g l a s s  syringes  (jaques e t a l . - 19U6). U.  Haematocrit E s t i m a t i o n W i n t r o b e * s m i x t u r e was u s e d as an a n t i c o a g u l a n t ,  o f b l o o d were spun f o r 30 m i n u t e s a t 2,210 R . C . F .  and t h e  samples  The samples u s e d were  p o r t i o n s o f t h e b l o o d o b t a i n e d f o r the b l o o d volume d e t e r m i n a t i o n s .  When  p o r t a l venous b l o o d was r e q u i r e d , a n e e d l e was i n s e r t e d d i r e c t l y i n t o portal vein.  the  I t was found t h a t c l o t s formed o f t e n i n t h i s p o r t i o n o f the  v e i n , and t h e r e f o r e  h e p a r i n was u s u a l l y g i v e n i n t h e s e e x p e r i m e n t s  (15 mgm/  k i l o o f body w e i g h t ) .  5>.  Acute L i g a t i o n o f tlie f t a r t a l  Vein  Under the s t a n d a r d c o n d i t i o n s d e s c r i b e d , the p o r t a l v e i n was identified,  and t h e o v e r l y i n g p e r i t o n e u m o f the f r e e edge o f the  sac d i v i d e d .  lesser  The v e i n was c l e a r e d upwards t o the b i f u r c a t i o n , and a b l a c k  s i l k l i g a t u r e a p p l i e d on the h e p a t i c s i d e o f the l a s t t r i b u t a r y , ends b r o u g h t o u t t h r o u g h t h e a b d o m i n a l wound.  and the  The t r a c t i o n n e c e s s a r y  to  expose the p o r t a l v e i n u s u a l l y caused v i o l e n t f l u c t u a t i o n s i n t h e b l o o d pressure,  and t i m e was a l l o w e d f o r t h i s t o r e t u r n t o n o r m a l .  pressure f i n a l l y s e t t l e d , as l i t t l e as p o s s i b l e .  When the  the l i g a t u r e was t i e d , d i s t u r b i n g t h e v i s c e r a  The a b d o m i n a l wound was c l o s e d w i t h A l l i s  and t h e dog l e f t u n d i s t u r b e d u n t i l  death.  When s i m u l t a n e o u s r e c o r d s were o b t a i n e d o f b o t h p r e s s u r e and p o r t a l venous p r e s s u r e ,  forceps,  intra-arterial  the a r t e r i a l p r e s s u r e was o b t a i n e d  u s i n g a mercury manometer as d e s c r i b e d a b o v e .  The p o r t a l venous p r e s s u r e  - 23 - • was o b t a i n e d b y c a n n u l a t i n g a s p l e n i c v e i n i n the g a s t r o - s p l e n i c  ligament,  u s i n g s i z e 16 p o l y t h e n e t u b i n g , and p a s s i n g the t u b i n g i n t o t h e main s p l e n i c vein.  The t u b i n g was t h e n c o n n e c t e d t o a p h y s i o l o g i c a l p r e s s u r e  transducer  (Statham model P 2 3 A ) , the o u t p u t b e i n g a m p l i f i e d b y a B r u s h u n i v e r s a l a m p l i fier  (Model B L 3 2 0 ) .  A c o n t i n u o u s i n k r e c o r d was o b t a i n e d b y means o f a  B r u s h o s c i l l o g r a p h (Model B L 2 0 2 ) .  The t u b i n g was f i l l e d w i t h s a l i n e , and  c l o t t i n g p r e v e n t e d b y h e p a r i n i z a t i o n o f the a n i m a l .  6.  E s t i m a t i o n o f B l o o d Volume The b l o o d volume d e t e r m i n a t i o n s were made u s i n g Reeve a n d V e a l l ' s  (19^9) m o d i f i c a t i o n f o r the p r o c e d u r e o f Hevesy and Zerahn ( 1 9 ^ 2 ) .  Ten  m l . o f venous b l o o d was w i t h d r a w n from a forepaw v e i n o f the dog i n t o a 10 ml. syringe containing heparin.  E i g h t m l . o f t h i s b l o o d was i n c u b a t e d w i t h  I4O m i c r o c u r i e s o f c a r r i e r f r e e P32 o f h i g h s p e c i f i c a c t i v i t y f o r a p p r o x i m a t e l y one and a h a l f hours i n a 10 m l . c e n t r i f u g e tube r o t a t e d i n a w a t e r b a t h at a constant temperature of 3 7 ° C .  The c e l l s were t h e n  from t h e plasma b y c e n t r i f u g i n g , and resuspended i n s a l i n e .  separated The s e p a r a t i o n  and r e s u s p e n s i o n was done t h r e e t i m e s .  Two m l . o f the f r e s h l y p r e p a r e d s u s p e n s i o n o f l a b e l l e d r e d c e l l s was i n j e c t e d i n t o a f e m o r a l v e i n .  A f t e r a l l o w i n g f i v e minutes f o r m i x i n g  t o o c c u r , 10 m l . o f b l o o d was w i t h d r a w n from the c o n t r a l a t e r a l f e m o r a l a r t e r y and p l a c e d i n a s m a l l g l a s s b e a k e r c o n t a i n i n g sodium c i t r a t e  crystals  as an a n t i c o a g u l a n t and powdered s a p o n i n t o produce l y s i s o f t h e r e d c e l l s . F i v e 1 m l . samples o f t h i s b l o o d were c o u n t e d s e p a r a t e l y f o r a c t i v i t y , u s i n g a g l a s s V e a l l r e - e n t r a n t type l i q u i d beta Geiger counter.  r  2k  -  The a c t i v i t y o f the specimen o f b l o o d withdrawn f r o m the  femoral  a r t e r y was compared w i t h t h e a c t i v i t y o f the o r i g i n a l 2 m l . s u s p e n s i o n labelled red c e l l s .  of  The a c t i v i t y o f t h i s was o b t a i n e d b y u s i n g the same  2 m l . s y r i n g e t o draw up the s u s p e n s i o n ,  and d i l u t i n g i t t o  approximately  the same volume as the b l o o d volume o f t h e dog b y i n j e c t i n g i t i n t o a W i n c h e s t e r b o t t l e c o n t a i n i n g 2000 m l . o f w a t e r , and a g a i n c o u n t i n g 5 samples o f 1 m l . o f the d i l u t i o n f o r  activity.  I f the t o t a l a c t i v i t y o f the per second,  l a b e l l e d r e d c e l l s i s A counts  and the a c t i v i t y o f 1 m l . o f t h e b l o o d withdrawn from  the  a n i m a l i s B c o u n t s per second t h e n t h e b l o o d volume, V , i s g i v e n b y  the  f o r m u l a BV = A , o r V • § .  was  required,  When a second b l o o d volume d e t e r m i n a t i o n  10 m l . o f b l o o d was w i t h d r a w n from t h e i p s i l a t e r a l  a r t e r y , and counted f o r background a c t i v i t y .  femoral  Immediately f o l l o w i n g the  w i t h d r a w a l , a f u r t h e r 2 m l . o f P32 l a b e l l e d r e d c e l l s was i n j e c t e d  into  the f e m o r a l v e i n n o t p r e v i o u s l y u s e d , and a g a i n , a f t e r $ m i n u t e s , 10 m l . o f b l o o d was o b t a i n e d from t h e f e m o r a l a r t e r y n o t p r e v i o u s l y u s e d . inserting  t h e n e e d l e (22 SWG) a t an a n g l e i n t o the a r t e r y , and b y  By finger  p r e s s u r e on the h o l e f o r t h r e e m i n u t e s a f t e r w i t h d r a w a l , no b l o o d escaped despite  7.  heparinization.  M i x i n g o f A c t i v a t e d Red C e l l s w i t h the C i r c u l a t i n g Red C e l l s . I n o r d e r t o d i s c o v e r whether adequate t i m e was a l l o w e d f o r  m i x i n g o f the i n j e c t e d r e d c e l l s w i t h the c i r c u l a t i n g r e d c e l l s , t y p e s o f e x p e r i m e n t s were c a r r i e d (a)  S e r i a l E s t i m a t i o n o f the  two  out. Activity  A two-way s t o p - c o c k a t t a c h e d t o an 18 SWG n e e d l e was  inserted  i n t o the l e f t f e m o r a l a r t e r y .  Two m l . o f P32 a c t i v a t e d r e d c e l l s were  i n j e c t e d i n t o the r i g h t femoral v e i n .  A t 2 minute i n t e r v a l s  thereafter  2 m l . samples o f b l o o d were o b t a i n e d from the f e m o r a l a r t e r y .  Before  each sample was c o l l e c t e d , 1 m l . was a l l o w e d t o f l o w t h r o u g h t h e n e e d l e and s t o p - c o c k t o f l u s h o u t t h e b l o o d r e m a i n i n g from t h e p r e v i o u s To o b v i a t e c l o t t i n g w i t h i n t h e n e e d l e ,  (b)  sample.  h e p a r i n was g i v e n t o the d o g .  Continuous Record o f A c t i v i t y The f e m o r a l v e s s e l s  on b o t h s i d e s were e x p o s e d .  On one  side  the f e m o r a l a r t e r y was d i v i d e d and c a n n u l a t e d w i t h No. 16 p o l y e t h y l e n e t u b i n g f i l l e d w i t h h e p a r i n i z e d s a l i n e , and a r r a n g e d so t h a t a h e l i x was formed, t h r o u g h w h i c h t h e b l o o d f l o w e d .  The h e l i x was p l a c e d between  two s e l f - q u e n c h i n g t h i n end window G e i g e r - M u l l e r c o u n t e r s , p a r a l l e l ( T r a c e r L a b . TGC-2). i n j e c t e d i n t o the c o n t r a l a t e r a l meter ( N u c l e a r i n s t r u m e n t  wired i n  Two m l . o f P32 l a b e l l e d r e d c e l l s were femoral v e i n .  By means o f a r a t e  c o r p o r a t i o n , Model l 6 l 5 - B ) a r r a n g e d t o r e c o r d  t h r o u g h an E s t e r l i n e Angus g r a p h i c ammeter r e c o r d e r ,  a  continuous  r e c o r d o f the l e v e l o f a c t i v i t y o f t h e c i r c u l a t i n g b l o o d c o u l d be obtained.  I n o r d e r t o check the p a t e n c y o f t h e system, a b l e e d i n g  t a p was p l a c e d on the d i s t a l s i d e o f t h e h e l i x . to prevent c l o t t i n g w i t h i n the 8.  H e p a r i n was g i v e n  tubing.  D e t e r m i n a t i o n o f Communications Between the P o r t a l and S y s t e m i c Venous C i r c u l a t i o n s As p r e v i o u s l y d e s c r i b e d ,  pentobarbital,  dogs were a n a e s t h e t i z e d w i t h sodium  t h e abdomen opened, and the p o r t a l v e i n l i g a t e d t o  raise  t h e p o r t a l venous p r e s s u r e , t h u s opening up any s m a l l anastomoses w i t h the systemic c i r c u l a t i o n .  A f t e r U5 minutes the dogs were k i l l e d b y  - 26 removing t h e a n t e r i o r c h e s t w a l l , d i v i d i n g the t h o r a c i c a o r t a , b l o o d t o f l o w from b o t h e n d s .  and a l l o w i n g  H e p a r i n was g i v e n p r i o r t o l i g a t i o n o f the  p o r t a l v e i n (5 m g m / k i l o o f body w e i g h t ) i n o r d e r t o p r e v e n t b l o c k a g e o f the s m a l l e r v e s s e l s w i t h c l o t s . then c u t . water t a p .  The l i g a t u r e around the p o r t a l v e i n was  A c a n n u l a was p l a c e d i n t h e t h o r a c i c a o r t a and a t t a c h e d t o a A t a p r e s s u r e o f 150-200 mm. o f mercury t h e b l o o d w i t h i n the  v e s s e l s was washed o u t , d r a i n a g e b e i n g p r o v i d e d b y a c a n n u l a w i t h i n i n f e r i o r vena c a v a , and a n o t h e r i n t h e p o r t a l v e i n . u n t i l the water r e t u r n e d c l e a r .  the  Washing was c o n t i n u e d  T h i s u s u a l l y took about one h o u r .  w a t e r was t h e n a l l o w e d t o d r a i n o u t and two hours l a t e r ,  latex  The  (Guttapercha  L 1 8 0 l a t e x s o l u t i o n ) was i n j e c t e d t h r o u g h the c a n n u l a w i t h i n t h e p o r t a l v e i n a t a c o n s t a n t p r e s s u r e o f 1 0 0 mm. o f m e r c u r y .  The i n j e c t i o n m a t e r i a l  f l o w e d q u i c k l y and e a s i l y t o f i l l a l l t h e s m a l l v e n u l e s o f t h e venous s y s t e m .  I n o r d e r t o be c e r t a i n o f f i l l i n g a l l v e s s e l s , the i n j e c t i o n  was m a i n t a i n e d a t t h i s p r e s s u r e f o r one h o u r . injection,  portal  A t the c o n c l u s i o n o f the  the p o r t a l v e i n c a n n u l a was c l o s e d , and the a n i m a l k e p t o v e r -  n i g h t t o a l l o w the l a t e x t o s e t .  I t was t h e n c a r e f u l l y d i s s e c t e d ,  the  symphysis p u b i s b e i n g d i v i d e d , and the p e l v i s d i s t r a c t e d and opened l i k e a s h e l l to d i s p l a y a l l p e l v i c communications.  The diaphragm was n o t  i n c i s e d p r i o r to i n j e c t i o n , b u t t h i s d i d not i n t e r f e r e w i t h the o f the communications a t the l o w e r end o f the  9.  filling  oesophagus.  Measurement o f S p l a n c h n i c B l o o d Volume When the c i r c u l a t i n g b l o o d volume i s e s t i m a t e d u s i n g  labelled  r e d c e l l s , t h e i n j e c t e d c e l l s a r e e q u a l l y d i s t r i b u t e d t h r o u g h o u t the b l o o d o f the r e c i p i e n t .  I f d u r i n g the measurement,  the f e e d i n g a r t e r i e s  and  d r a i n i n g v e i n s o f any organ a r e s i m u l t a n e o u s l y o c c l u d e d , the b l o o d v e s s e l s  - 27 o f the organ w i l l c o n t a i n t h e i r n o r m a l q u o t a o f b l o o d , and a p r o p o r t i o n o f the r e d c e l l s w i l l show a c t i v i t y . t h a t organ w i l l t h e r e f o r e  A measure o f the t o t a l a c t i v i t y o f  give the q u a n t i t y of b l o o d contained w i t h i n  the  organ. Pound dogs a n a e s t h e t i z e d w i t h sodium p e n t o b a r b i t a l were u s e d .  intravenously  Ten m l . o f b l o o d was o b t a i n e d from the r i g h t f e m o r a l v e i n f o r  incubation with P ^ *  A f t e r a p p r o x i m a t e l y one and a h a l f h o u r s , t h e  men was opened, and l i g a t u r e s were p l a c e d around t h e  abdo-  intra-abdominal  oesophagus and around the rectum as c l o s e t o the a n a l c a n a l as p o s s i b l e , and t i e d .  The c o e l i a c a x i s and g r e a t m e s e n t e r i c a r t e r y were i d e n t i f i e d ,  and w i t h the minimum o f d i s s e c t i o n were c l e a r e d so t h a t a heavy haemostat c o u l d o c c l u d e them.  S i m i l a r l y , the p o r t a l v e i n was i d e n t i f i e d and c l e a r e d .  The l e s s e r m e s e n t e r i c a r t e r y was c l e a r e d , l i g a t e d and d i v i d e d .  The c i r c u -  l a t i n g b l o o d volume was e s t i m a t e d i n the u s u a l manner w i t h t h e i n j e c t i o n o f 2 m l . P^2 l a b e l l e d r e d c e l l s .  Immediately f o l l o w i n g w i t h d r a w a l o f t h e  sample o f b l o o d f o r d e t e r m i n a t i o n o f t h e b l o o d volume, clamps were a p p l i e d s i m u l t a n e o u s l y t o the p o r t a l v e i n and g r e a t m e s e n t e r i c a r t e r y .  By d i v i d i n g  t h e s e v e s s e l s , c u t t i n g a c r o s s t h e oesophagus and r e c t u m , and c u t t i n g  the  a t t a c h m e n t o f the mesentery t o the p o s t e r i o r a b d o m i n a l w a l l and o f the l e s s e r omentum t o the l i v e r ,  i t was b u t a moment's e f f o r t t o remove  the  whole o f the i n t r a - a b d o m i n a l g a s t r o - i n t e s t i n a l t r a c t from the l o w e r oesophagus t o the l o w e s t p a r t o f the r e c t u m , t o g e t h e r w i t h s p l e e n and p a n c r e a s , w i t h o u t l o s i n g any o f t h e c o n t a i n e d b l o o d . T h e s e organs were t h e n p l a c e d i n a l a r g e j a r and c o n c e n t r a t e d h y d r o c h l o r i c a c i d added t o render the contents  i n t o a homogeneous l i q u o r .  This process  took  a p p r o x i m a t e l y U8 hours d u r i n g w h i c h time the decay o f r a d i o a c t i v e  - 28 phosphorus o c c u r r e d a t a known r a t e .  The f a t r o s e t o t h e s u r f a c e and was  d i s c a r d e d , f o r i t c o n t a i n s o n l y about 1% o f t h e a c t i v i t y compared w i t h an equal quantity of l i q u o r .  The d i m i n u t i o n o f c o u n t i n g r a t e w h i c h o c c u r s  due t o s e l f - a b s o r p t i o n when t h i s l i q u o r i s u s e d , compared w i t h the c o u n t i n g rate i n water,  i s only 3.3$.  The s p e c i f i c g r a v i t y o f t h e l i q u o r i n t h r e e  e x p e r i m e n t s was 1 . 1 1 5 , 1.116 and 1.086, a f t e r  the f a t had been skimmed o f f .  The volume o f t h e l i q u o r was measured and c o u n t s were t h e n made o f t h e a c t i v i t y o f 10 m l . s a m p l e s .  Having c o r r e c t e d f o r the n a t u r a l decay o f t h e  a c t i v i t y o f the r a d i o a c t i v e phosphorus, t h e t o t a l a c t i v i t y c o n t a i n e d w i t h i n t h e i n t r a - a b d o m i n a l g a s t r o - i n t e s t i n a l t r a c t was o b t a i n e d .  I f the  total  a c t i v i t y o f t h e i n j e c t e d P32 l a b e l l e d r e d c e l l s i s A counts p e r second and the a c t i v i t y o f 1 m l . o f the b l o o d w i t h d r a w n from t h e a n i m a l a f t e r  mixing  has o c c u r r e d i s B counts p e r s e c o n d , t h e n t h e t o t a l c i r c u l a t i n g b l o o d volume V i s g i v e n b y the f o r m u l a BV » A .  A l s o i f the a c t i v i t y o f t h e  l i q u o r o f t h e d i g e s t e d organs i s X counts p e r second p e r m l . , and the  total  volume i s Y , t h e n the t o t a l a c t i v i t y o f t h e l i q u o r i s XY c o u n t s p e r s e c o n d . By s i m p l e p r o p o r t i o n , i f t h e volume o f t h e b l o o d c o n t a i n e d w i t h i n  the  d i g e s t e d organs i s V I t h e n Vi „ — V  XY — A  or  ^ XY x V Vn = A  OBSERVATIONS 1.  Acute L i g a t i o n o f the P o r t a l V e i n (a)  Length o f S u r v i v a l F o l l o w i n g Acute L i g a t i o n Table I shows the s u r v i v a l t i m e f o l l o w i n g a c u t e l i g a t i o n under  three d i f f e r e n t circumstances, only,  ( i ) acute l i g a t i o n o f the p o r t a l v e i n  ( i i ) acute l i g a t i o n of the p o r t a l v e i n , together w i t h l i g a t i o n  o f t h e oesophageal a n a s t o m o t i c v e i n s ,  ( i i i ) a c u t e l i g a t i o n o f the  -  29 -  p o r t a l v e i n , t h e dogs b e i n g g i v e n h e p a r i n .  Discussion. A c u t e l i g a t i o n i n lU dogs caused d e a t h i n a n average o f 79.7 + (- 18.9) minutes, a f i g u r e which i s i n accord w i t h t h a t recorded i n the l i t e r a t u r e .  When, i n a d d i t i o n , a l i g a t u r e was p l a c e d around the  i n t r a - a b d o m i n a l oesophagus i n 11 d o g s , the t i m e o f s u r v i v a l was s h o r t e n e d to 56.0 (- 8.5) minutes.  I n 9 dogs w i t h a c u t e l i g a t i o n o f t h e p o r t a l  v e i n , w i t h o u t o e s o p h a g e a l l i g a t u r e , b u t g i v e n h e p a r i n (10 m g s / k g ) , t i m e o f s u r v i v a l was 8 8 . 6 ( - 23.26) m i n u t e s .  There was a s i g n i f i c a n t  d i f f e r e n c e between the l e n g t h o f s u r v i v a l w i t h o r w i t h o u t oesophageal l i g a t u r e s , b u t no d i f f e r e n c e between s u r v i v a l w i t h o r w i t h o u t h e p a r i n . I n f o u r dogs t h e l i g a t u r e was p l a c e d on the i n t e s t i n a l s i d e o f a p a n c r e a t i c o - g a s t r i c v e i n , and was t h e r e f o r e dogs s u r v i v e d , and were k i l l e d a f t e r  incomplete.  two h o u r s .  Two o f t h e s e  I n one, the  tributary  measured 1.5 mm. i n d i a m e t e r , and the s y s t e m i c b l o o d p r e s s u r e a t s a c r i f i c e was 90 mm. H g .  Of the o t h e r two dogs w h i c h d i e d , one was an  o l d d o g , w i t h a t r i b u t a r y measuring 1.5 mm., the o t h e r was a young d o g , w i t h a t r i b u t a r y measuring 0 . 5 mm. i n d i a m e t e r . (b)  O b s e r v a t i o n s on B l o o d P r e s s u r e I m m e d i a t e l y f o l l o w i n g l i g a t i o n o f the p o r t a l v e i n the  arterial  p r e s s u r e drops r a p i d l y i n the f i r s t few minutes and t h e n more s l o w l y t o r e a c h a p l a t e a u a t 30-U0 mm. H g . a f t e r  about 19-20 m i n u t e s .  It  s t a y s a t t h i s l e v e l w i t h o n l y minor f l u c t u a t i o n s u n t i l j u s t p r i o r t o death.  - 30 If  s i m u l t a n e o u s r e c o r d s a r e t a k e n o f the p o r t a l venous p r e s s u r e  and a r t e r i a l p r e s s u r e i t i s shown t h a t t h e p o r t a l venous p r e s s u r e  rises  from a p r e l i g a t i o n l e v e l o f around 7 mm. H g . t o a maximum o f 50-60 mm. Hg. i n about 2 m i n s ; t h e r e a f t e r t h e p o r t a l venous p r e s s u r e  declines  p a r a l l e l i n g t h e f a l l i n the s y s t e m i c a r t e r i a l p r e s s u r e t o a l e v e l m i d way between the d i a s t o l i c and s y s t o l i c p r e s s u r e s .  A typical result  is  shown i n F i g . I .  Discussion. Following l i g a t i o n , blood i s continuously supplied to splanchnic vessels,  from w h i c h i t c a n n o t e s c a p e .  b l o o d volume i s r a p i d l y r e d u c e d , fall,  the  As t h e c i r c u l a t i n g  so t h e s y s t e m i c b l o o d p r e s s u r e  will  u n t i l i t i s e q u a l t o the l e v e l t o w h i c h t h e p o r t a l venous p r e s s u r e  rises.  W h i l e the p r e s s u r e s r e m a i n e q u a l , d u r i n g the p e r i o d o f  plateau,  the  the o n l y b l o o d e n t e r i n g the s p l a n c h n i c v a s c u l a r bed w i l l be  t o r e p l a c e t h e b l o o d e s c a p i n g from t h e b e d b y the  porto-systemic  anastomoses, and the b l o o d l o s t b y haemorrhage i n t o the b o w e l w a l l . The s p l a n c h n i c bed i s t o a l l i n t e n t s e x c l u d e d from the c i r c u l a t i o n . I f the p o r t o - s y s t e m i c complete.  anastomoses a r e o c c l u d e d the e x c l u s i o n i s more  T h e r e f o r e a measurement o f t h e b l o o d volume d u r i n g  p e r i o d w i l l measure o n l y t h e c i r c u l a t i n g s y s t e m i c It i s interesting  portion.  t o n o t e t h a t t h e r e i s no a p p a r e n t a t t e m p t t o  compensate f o r the p o o l i n g o f t h e b l o o d w i t h i n t h e s p l a n c h n i c lation.  this  There a r e two p o s s i b l e e x p l a n a t i o n s ,  circu-  ( i ) any a t t e m p t b y the  dog t o compensate f o r t h e f a l l i n g b l o o d volume b y v a s o c o n s t r i c t i o n w i l l r a i s e the p r e s s u r e , w h i c h w i l l cause f u r t h e r  b l o o d t o be l o s t  into  - 31 the splanchnic b e d . this,  The b l o o d p r e s s u r e r e c o r d s show no e v i d e n c e o f  ( i i ) compensation may f a i l t o o c c u r .  Peck and G r o v e r ( l ° 5 2 )  have s u g g e s t e d t h a t the i n i t i a l r a p i d f a l l i n a r t e r i a l p r e s s u r e i s r e f l e x i n n a t u r e , w h i l e t h e e n s u i n g s l o w e r f a l l i s due t o a d e c l i n e i n c i r c u l a t i n g b l o o d volume.  They s t a t e d t h a t i t was n o t p o s s i b l e f o r  t h e r e d u c t i o n i n b l o o d volume t o be so g r e a t as t o produce s u c h a  fall  i n b l o o d p r e s s u r e i n t h e t i m e r e c o r d e d , b u t t h i s p o s s i b i l i t y c a n n o t be e x c l u d e d u n t i l t h e r e d u c t i o n i n b l o o d volume, and t h e r a t e a t w h i c h i t proceeds,  2.  i s known.  B l o o d Volume E s t i m a t i o n s The r e s u l t s o f e l e v e n experiments a r e summarized i n T a b l e I I .  F o l l o w i n g sodium p e n t o b a r b i t a l a n a e s t h e s i a and the trauma a t t e n d a n t on t h e abdominal i n c i s i o n , t h e average c i r c u l a t i n g b l o o d volume was  76.9  (1 6.55) m l . p e r k i l o g r a m body w e i g h t .  T h i r t y minutes a f t e r  occlusion  o f the p o r t a l v e i n and 10 m i n u t e s a f t e r  l i g a t i o n o f t h e oesophagus and  i t s v e s s e l s , t h e average s y s t e m i c c i r c u l a t i n g volume was 32.7 (-  8.23)  m l . p e r k i l o g r a m , a r e d u c t i o n o f hk.2 m l / k g . o r 57.9$ (± 8.77) o f  the  o r i g i n a l blood volume. Table I I I l i s t s the t r u e c o u n t s p e r second p e r 10 m l . u t i l i z i n g the c o n s t a n t geometry p r o v i d e d b y t h e same V e a l l c o u n t e r f o r each o f 5 c o u n t s f o r each e x p e r i m e n t .  F o l l o w i n g l i g a t i o n o f the p o r t a l v e i n ,  the  average c o u n t i n g r a t e o f t h e s y s t e m i c b l o o d f e l l t o 85.0$ (- 13.8) o f t h e p r e - l i g a t i o n v a l u e , w h i l e - t h e p o r t a l venous count r o s e t o 117.2% (* 15.9) of i t s o r i g i n a l v a l u e .  F i v e minutes a f t e r the second i n j e c t i o n o f l a b e l l e d  r e d c e l l s , t h e average c o u n t i n g r a t e o f t h e p o r t a l venous b l o o d r o s e o n l y  - 32 * 1.3$ ( - 7.5$) above t h e b a c k g r o u n d count f o r the b l o o d i m m e d i a t e l y p r i o r t o t h e second i n j e c t i o n , whereas the average s y s t e m i c c o u n t r o s e 178.8$ (i 8 0 . 2 ) .  I n a p r e l i m i n a r y s e r i e s o f seven dogs, a s i m i l a r type o f e x p e r i ment was u n d e r t a k e n , e x c e p t t h a t the p o r t a l v e i n o n l y was l i g a t e d and c o l l a t e r a l v e s s e l s were i g n o r e d .  A f t e r the second i n j e c t i o n o f P32 l a b e l l e d  r e d c e l l s a r i s e i n t h e average p o r t a l venous b l o o d c o u n t i n g r a t e o f 17.8$ ( - 2 2 . 2 ) was n o t e d , when t h e average s y s t e m i c b l o o d c o u n t i n g r a t e r o s e 175.6$ ( i 5 3 . 0 ) .  T h i s i n d i c a t e d t h e degree o f l e a k a g e o f l a b e l l e d r e d  c e l l s i n t o t h e s p l a n c h n i c v a s c u l a r b e d , when t h e s e main a n a s t o m o t i c c h a n n e l s were n o t o c c l u d e d .  ,  I t was as a consequence o f the p r e l i m i n a r y e x p e r i m e n t s t h a t  the  s i t u a t i o n o f t h e main anastomoses between the s y s t e m i c and p o r t a l venous c i r c u l a t i o n s was i n v e s t i g a t e d , as w i l l be d e s c r i b e d l a t e r .  Discussion. I t i s p o s s i b l e t o c a r r y out a c c u r a t e d e t e r m i n a t i o n s o f c i r c u l a t i n g b l o o d volumes b y u s i n g r e d b l o o d c e l l s l a b e l l e d w i t h r a d i o a c t i v e phosphorus (P32) (Hevesy and Zerahn - 19U2). were made u s i n g Reeve and V e a l l ' s Hevesy and Z e r a h n .  I n t h i s e x p e r i m e n t the  determinations  (I9k9) m o d i f i c a t i o n o f t h e method o f  B y u s i n g the V e a l l c o u n t e r , i t i s n o t n e c e s s a r y  to  e s t i m a t e t h e h a e m a t o c r i t t o c a l c u l a t e b l o o d volume, f o r t h e a c t i v i t y o f whole b l o o d i s c o u n t e d , and i t i s u n n e c e s s a r y t o a p p l y any c o r r e c t i o n f a c t o r f o r plasma t r a p p e d w i t h t h e r e d b l o o d  cells.  F i g u r e s f o r the c i r c u l a t i n g b l o o d volume o f dogs have been g i v e n by s e v e r a l o b s e r v e r s , Table I V .  - 33 -  I n g e n e r a l , i n human p a t i e n t s the v a l u e g i v e n b y the P^2 method has been f o u n d t o b e l o w e r t h a n t h a t b a s e d on t h e dye T-1821+.  The v a l u e  f o r dogs o b t a i n e d i n t h e s e e x p e r i m e n t s ( 7 6 . 9 m l / k g ) i s r e m a r k a b l y c o n s i s t e n t , b u t n e v e r t h e l e s s i t cannot be compared w i t h t h o s e g i v e n b y o t h e r w o r k e r s , f o r i t was o b t a i n e d a f t e r  the trauma o f opening t h e abdomen.  B o t h Hahn e t a l . (191+2) and Delorme e t a l . (1952) have  stated  t h a t m i x i n g o f the l a b e l l e d r e d c e l l s i n the c i r c u l a t i o n i s complete w i t h i n k minutes f o l l o w i n g i n j e c t i o n .  F i g u r e I I shows t h e m i x i n g c u r v e s i n two  experiments a f t e r the i n j e c t i o n o f 2 m l . o f P-j l a b e l l e d red c e l l s , 2  c o r r e c t e d c o u n t s o f a c t i v i t y b e i n g o b t a i n e d b y 2 m l . samples o f b l o o d w i t h d r a w n a t t h e t i m e s shown.  M i x i n g i s b a r e l y complete i n 5 m i n u t e s .  The a c t i v i t y o f the i n j e c t e d c e l l s does n o t remain c o n s t a n t b u t shows a p e r s i s t e n t s t e a d y d e c l i n e as has been f o u n d b y o t h e r i n v e s t i g a t o r s (Hahn e t a l . - 191+2, K r i e g e r e t a l . - 191+8, Reeve and V e a l l - 191+9), and i n c o n t r a d i s t i n c t i o n t o Delorme e t a l . -  (l95l).  F i g u r e I I I shows s i m i l a r r e s u l t s u s i n g thejnethod o f c o n t i n u o u s r e c o r d s o f the c o u n t i n g r a t e employing the end window G e i g e r c o u n t e r s and a r a t e meter r e c o r d i n g t h r o u g h an E s t e l i n e Angus r e c o r d e r .  Again  m i x i n g i s shown . t o be b a r e l y complete i n 5 m i n u t e s .  F o l l o w i n g l i g a t i o n o f the p o r t a l v e i n , w i t h the  sequestration  of b l o o d w i t h i n the p o r t a l v a s c u l a r bed, mixing of i n j e c t e d l a b e l l e d r e d c e l l s w i t h t h e s y s t e m i c c i r c u l a t i n g b l o o d i s s l o w e d , due t o t h e r e d u c e d c a r d i a c o u t p u t and r e d u c e d b l o o d f l o w .  F i g u r e I V shows the r a t e o f  m i x i n g o c c u r r i n g i n t h e s y s t e m i c c i r c u l a t i o n a t i n t e r v a l s , f o r 20 minutes after  i n j e c t i o n o f P 3 2 l a b e l l e d r e d c e l l s i n two e x p e r i m e n t s .  The r e d  - 3h c e l l s were i n j e c t e d 20 minutes a f t e r  t h e p o r t a l v e i n was l i g a t e d .  Again,  m i x i n g i s b a r e l y complete a f t e r $ m i n u t e s , b u t t h e c o u n t i n g r a t e s t a r t s t o f a l l b y the t e n t h m i n u t e .  I t i s during t h i s short period that i t  is  n e c e s s a r y t o w i t h d r a w the b l o o d t o a v o i d t h e e r r o r - on t he one hand, o f i n c o m p l e t e m i x i n g ; on t h e o t h e r ,  of the d e c l i n e i n the counting rate  r e s u l t i n g from b o t h the s e q u e s t r a t i o n w i t h i n t h e s p l a n c h n i c v a s c u l a r bed and t h e n o r m a l l y o c c u r r i n g d e c r e a s e i n c o u n t i n g r a t e .  The i n j e c t i o n o f P32 l a b e l l e d r e d c e l l s f o r the second b l o o d volume d e t e r m i n a t i o n was made i n t o the i n f e r i o r vena cava and t h e  systemic  sample t a k e n from t h e f e m o r a l a r t e r y i n o r d e r t o a t t e m p t t o reduce  the  e f f e c t o f s l u g g i s h p e r i p h e r a l f l o w (Gregersen and Rawson - 19^2).  The  e r r o r i n t r o d u c e d b y i n c o m p l e t e m i x i n g w i l l be s u c h t h a t d i l u t i o n w i l l  not  be c o m p l e t e d , and thus t o o l o w a v a l u e f o r the c i r c u l a t i n g b l o o d volume w i l l be o b t a i n e d .  As the e r r o r i s l i k e l y t o be g r e a t e r i n the second b l o o d  volume e s t i m a t i o n t h a n i n the f i r s t , t h e v a l u e s o b t a i n e d f o r t h e decrease i n c i r c u l a t i n g b l o o d volume are l i k e l y t o be t o o g r e a t .  The e s t i m a t i o n o f the c i r c u l a t i n g b l o o d volume was made 30 minutes a f t e r t h e o c c l u s i o n o f the p o r t a l v e i n d u r i n g t h e p e r i o d o f the b l o o d p r e s s u r e p l a t e a u and about midway i n the time o f s u r v i v a l . b l o o d c o n t i n u e d t o be l o s t i n t o the b o w e l , t h i s was t o some e x t e n t  Though offset  by the r e t u r n o f b l o o d from t h e s p l a n c h n i c b e d as the a r t e r i a l p r e s s u r e declined p r i o r to death,  and p o s s i b l y b y plasma r e t u r n e d from t h e b o w e l  b y the l y m p h a t i c s .  These e x p e r i m e n t s have shown t h a t t h e r e d u c t i o n i n c i r c u l a t i n g b l o o d volume f o l l o w i n g sudden and a c u t e l i g a t i o n o f the p o r t a l v e i n i s  - 35 -  57.9$ o f t h e o r i g i n a l v o l u m e , b u t t h i s v a l u e cannot be compared w i t h t h o s e o b t a i n e d b y Elman and C o l e (1932) o r Boyce and o t h e r s (1935).  Their values  r e f l e c t e d o n l y the q u a n t i t y o f b l o o d i n t r o d u c e d i n t o t h e s p l a n c h n i c v a s c u l a r b e d and i g n o r e d t h a t p o r t i o n n o r m a l l y c o n t a i n e d w i t h i n t h e  vessels  of the b e d .  An e x p e r i m e n t s i m i l a r i n d e s i g n t o the one d e s c r i b e d i n t h i s t h e s i s was p e r f o r m e d b y M a l l e t - G u y , D e v i c and Gangolphe (1950). Unfortunately t h e y chose the dye method t o e s t i m a t e  the b l o o d volume.  T h i s meant  that  U8 hours had t o e l a p s e between the f i r s t and second b l o o d volume e s t i m a t i o n s ^ t o a l l o w the dye o f t h e f i r s t e s t i m a t i o n t o d i s a p p e a r , was p r o b a b l y n o t l o n g enough.  though e v e n t h i s  Because t h e y c o u l d n o t f i n d  thiocyanate,  s u b t o s a n o r methylene b l u e i n t h e p o r t a l v e i n when i t was i n j e c t e d s y s t e m i c a l l y after  p o r t a l v e i n l i g a t i o n , t h e y i g n o r e d the c o l l a t e r a l p a t h s .  t h i s i s not j u s t i f i e d .  But  M o r e o v e r , t h e y made no m e n t i o n o f the d e t a i l s o f  t h e i r methods p a r t i c u l a r l y d u r i n g t h e second e s t i m a t i o n .  Finally,  the  v a l u e t h e y o b t a i n e d o f a r e d u c t i o n i n c i r c u l a t i n g b l o o d volume o f 1+9.3$ i s n o t comparable t o t h a t o f Elman and C o l e (1932) o r Boyce e t a l . (1935) f o r i t too i n c l u d e s the b l o o d normally present i n the s p l a n c h n i c v a s c u l a r bed.  The comparable f i g u r e i s 36.7$ as w i l l be seen  later.  I n o r d e r t o d i s c o v e r whether c o n s e c u t i v e e s t i m a t i o n s o f b l o o d volume c o u l d be made u s i n g the P32 method, two e x p e r i m e n t s were c a r r i e d o u t , and t h e r e s u l t s a r e f o u n d i n T a b l e V .  I n the f i r s t experiment,  second d e t e r m i n a t i o n f o l l o w e d i m m e d i a t e l y a f t e r minutes a f t e r  the s e c o n d .  the  the f i r s t , the t h i r d 30  The d i f f e r e n c e s were 3.1$ and 2.2$ r e s p e c t i v e l y .  I n t h e second e x p e r i m e n t , t h e second d e t e r m i n a t i o n f o l l o w e d i m m e d i a t e l y  -36a f t e r the f i r s t and t h e d i f f e r e n c e was 3.1$ 3.  E s t i m a t i o n s o f S p l a n c h n i c B l o o d Volume The r e s u l t s a r e shown i n T a b l e V I .  The c i r c u l a t i n g b l o o d volume  i n t h e s e 10 dogs was 8 l . l ( - 17,h) m l . p e r k g . compared t o t h e f i g u r e o f 76.9 (£ 6.55)  m l . per k g .  previous  The s p l a n c h n i c b l o o d volume, t h a t i s ,  the b l o o d contained w i t h i n the v e s s e l s  o f the i n t e s t i n e s ,  from c a r d i a  to  r e c t u m , t o g e t h e r w i t h t h e s p l e e n and p a n c r e a s , was found t o be 1 7 . 7 ( m l . p e r k g . body w e i g h t .  T h i s r e p r e s e n t s 2 1 . 7 ( - 5.5)  5.9)  % o f the c i r c u l a t i n g  b l o o d volume.  Discussion. Mass l i g a t i o n o f t h e oesophagus w i l l o c c l u d e the main anastomosis between t h e s y s t e m i c and p o r t a l venous systems, b u t p r o v i d e d t h e v e i n i s not obstructed, w i t h i n the v i s c e r a .  portal  i t w i l l not l e a d to increased p o o l i n g of b l o o d  L i g a t i o n o f the l o w e r r e c t u m i n t e r r u p t s even fewer  anastomoses, and l i g a t i o n o f t h e l e s s e r m e s e n t e r i c  a r t e r y probably reduces  t h e i n f l o w b y v e r y l i t t l e i n p r o p o r t i o n t o t h e g r e a t amount o f b l o o d p r o v i d e d from the c o e l i a c a x i s .  arterial  The s p l e e n i n t h e s e dogs remained  r e m a r k a b l y c o n s t a n t i n s i z e p r o v i d e d t h a t g r o s s m a n i p u l a t i o n was a v o i d e d , p r o b a b l y as a r e s u l t o f the sodium p e n t o b a r b i t a l a n a e s t h e s i a , though u n d o u b t e d l y the q u a n t i t y o f b l o o d c o n t a i n e d v a r i e d from dog t o d o g .  It  is  e a s y t o a p p l y t h e clamps t o c o e l i a c a x i s and p o r t a l v e i n s i m u l t a n e o u s l y s o t h a t t h e e r r o r s o f uncompensated  d r a i n a g e b y the p o r t a l o u t l e t ,  g e s t i o n from o b s t r u c t i o n t o the p o r t a l o u t l e t can be a v o i d e d . the i n t e s t i n e s  or con-  Removal o f  i s p o s s i b l e w i t h o u t any escape o f t h e c o n t a i n e d b l o o d .  - 37 The o n l y o t h e r comparable f i g u r e s a r e t h o s e produced b y Delorme e t a l . (1951) u s i n g the  " e x c l u s i o n " method.  "The method o f measuring  c i r c u l a t i n g b l o o d volume b y l a b e l l i n g e r y t h r o c y t e s w i t h r a d i o a c t i v e  isotope  may be m o d i f i e d t o measure t h e volume o f a p a r t o f t h e c i r c u l a t i o n b y e x c l u d i n g t h a t p a r t from t h e g e n e r a l c i r c u l a t i o n i m m e d i a t e l y b e f o r e i n j e c t i o n of l a b e l l e d corpuscles measured,  ( N y l i n - 191+7).  the  The b l o o d volume so  i s the t o t a l b l o o d volume l e s s t h a t o f t h e e x c l u d e d s e c t i o n .  When t h e e x c l u d e d a r e a i s opened, the b l o o d i n w h i c h t h e r e are no l a b e l l e d c o r p u s c l e s mixes w i t h and d i l u t e s t h e r a d i o a c t i v e b l o o d i n the circulation.  general  T h i s d i l u t i o n i s a m a t t e r o f t h e volume o f the e x c l u d e d s e c t i o n ! '  I n t h e i r e x p e r i m e n t s the s p l a n c h n i c b e d was t a k e n as stomach, s p l e e n , p a n c r e a s and l i v e r .  intestines,  T h i s was e s t i m a t e d t o c o n t a i n between 20$ and  50$ o f t h e t o t a l b l o o d volume i n . 13 dogs, w i t h an average o f 3U.8$.  While  t h i s method has the advantage o f n o t r e q u i r i n g the e v i s c e r a t i o n o f the dog, i t i s s u b j e c t t o the s e r i o u s e r r o r o f t h e escape o f l a b e l l e d r e d c e l l s i n t o the excluded area by anastomotic  channels.  In addition, i t i s impossible  s i m u l t a n e o u s l y t o clamp b o t h t h e f e e d i n g and d r a i n i n g v e s s e l s o f constituent  the  components o f t h e i r s p l a n c h n i c v a s c u l a r b e d , and t h u s a c o n -  s i d e r a b l e e r r o r from e i t h e r c o n g e s t i o n o r emptying o f the v e s s e l s  will  occur.  hepatic  I n t h r e e a n i m a l s t h e y e s t i m a t e d t h e volume i n the "proper  s u p p l y " t o be 16, 6 and 22$ o f t h e i r s p l a n c h n i c b l o o d v o l u m e .  In these  t h r e e dogs, t h e i r s p l a n c h n i c b l o o d volume was r e s p e c t i v e l y 50, 25 and 25$.  T h e r e f o r e , b y s u b t r a c t i n g the  "proper h e p a t i c s u p p l y " from t h e i r  s p l a n c h n i c b l o o d volume, f i g u r e s c o r r e s p o n d i n g t o our s p l a n c h n i c b l o o d volume a r e 1+1, 23 and 19$ r e s p e c t i v e l y .  - 38 I f t h e b l o o d volume o f t h e dog i s t a k e n as 76.9 m l / k g body w e i g h t and the b l o o d volume o f t h e s p l a n c h n i c v a s c u l a r bed i s 1 7 . 7 m l / k g body weight, then after  the s p l a n c h n i c v a s c u l a r bed has been e x c l u d e d ,  the  c a p a c i t y o f t h e r e m a i n i n g s y s t e m i c v a s c u l a r bed i s 5 9 . 2 m l / k g body w e i g h t . A f t e r l i g a t i o n o f t h e p o r t a l v e i n t h e s y s t e m i c c i r c u l a t i n g b l o o d volume i s r e d u c e d t o 3 2 . 7 m l / k g body w e i g h t .  I t can be argued t h a t the  r e d u c t i o n i n the c i r c u l a t i n g b l o o d volume i s t h e r e f o r e  the  true  difference  between t h i s f i g u r e and the v a l u e f o r t h e c i r c u l a t i n g b l o o d volume w i t h t h e s p l a n c h n i c bed e x c l u d e d , ( 5 9 . 2 m l / k g ) , t h a t i s , 2 6 . 4 m l / k g body w e i g h t o r 4 4 . 6 $ , f o r t h e r e m a i n i n g c i r c u l a t i n g b l o o d volume i s r e q u i r e d t o f i l l v a s c u l a r bed r e d u c e d by the normal c a p a c i t y o f the s p l a n c h n i c b e d . t h i s f i g u r e w h i c h c o r r e s p o n d s t o t h a t o f Elman & C o l e  4.  a  It  is  (1932).  Haematocrit E s t i m a t i o n s T a b l e V I I shows h a e m a t o c r i t r e s u l t s o b t a i n e d p r i o r t o and  f o l l o w i n g l i g a t i o n o f the p o r t a l v e i n . Discussion. The d i f f e r e n c e i n t h e h a e m a t o c r i t v a l u e s f o r b l o o d drawn from t h e f e m o r a l v e i n b e f o r e a n a e s t h e s i a w i t h sodium p e n t o b a r b i t a l , the femoral a r t e r y f o l l o w i n g anaesthesia are o f d o u b t f u l (p<^0.05).  and from  significance  I t i s n o t p o s s i b l e t o s a y w h i c h o f t h e two v a r i a b l e s  (the  source o f t h e b l o o d o r t h e p e n t o b a r b i t a l a n a e s t h e s i a ) i s t h e c a u s e . m i n u t e s and 40 minutes a f t e r  o c c l u s i o n o f the p o r t a l v e i n , the  Thirty  haematocrit  v a l u e s w i t h i n the a r t e r i a l system a r e seen t o have f a l l e n i n e v e r y case e x c e p t one.  T h i s f a l l i s h i g h l y s i g n i f i c a n t (p<^0.01).  The  haematocrit  v a l u e s o f t h e b l o o d w i t h i n t h e p o r t a l v e i n a r e seen t o have r i s e n t o a  - 39 h i g h l y s i g n i f i c a n t extent  (p ^  0.01).  The l a t t e r r e f l e c t s a c o n t i n u e d escape o f plasma i n t o t h e b o w e l wall.  The cause o f the c o n t i n u e d f a l l i n t h e a r t e r i a l h a e m a t o c r i t s  h a r d e r t o account f o r .  I t i s pertinent at t h i s point to discuss  effect of pentobarbital anaesthesia.  is  the  Ingraham e t a l . (1950) s t a t e d  that  p e n t o b a r b i t a l a n a e s t h e s i a i n t w o - t h i r d s o f t h e dose n o r m a l l y u s e d ( 2 1 . 4 mg/ k g body w e i g h t ) has no e f f e c t on the c o u r s e o f e v e n t s i n haemorrhagic s h o c k , but i t does, n e v e r t h e l e s s ,  cause enlargement o f t h e s p l e e n , produce  h a e m o d i l u t i o n , and cause c o n g e s t i o n o f t h e v i s c e r a (Wiggers - 1 9 4 2 ) .  These  o b s e r v a t i o n s have been s u p p o r t e d b y Wang and W a l c o t t (1952) who found t h e r e was no s i g n i f i c a n t change i n the f i n a l b l e e d i n g volume a f t e r pentobarbital anaesthesia,  and b y B o l l m a n e t a l . ( 1 9 3 8 ) , Hahn e t a l .  (1942) and C o u r t i c e and Gunton ( 1 9 4 9 ) , a l l o f whom found t h a t the was e n l a r g e d a f t e r p e n t o b a r b i t a l a n a e s t h e s i a .  Haussner e t a l . (1938)  a t t a c h e d l e a d s h o t s t o the s p l e e n , and b y x - r a y o b s e r v e d i t s after pentobarbital  spleen  enlargement  anaesthesia.  I n o r d e r t o see whether splenectomy w o u l d have any e f f e c t the c o u r s e o f e v e n t s a f t e r l i g a t i o n o f t h e p o r t a l v e i n , f o u r were done.  on  experiments  I n t w o , the abdomen was opened, t h e p o r t a l v e i n c l e a r e d and  a l i g a t u r e p l a c e d i n t h e u s u a l manner.  The s p l e n i c a r t e r y was l i g a t e d ,  and when t h e s p l e e n had s h r u n k , t h e s p l e n i c p e d i c l e was clamped and t h e s p l e e n e x c l u d e d from t h e c i r c u l a t i o n .  The p o r t a l v e i n was t h e n l i g a t e d  and t h e dogs d i e d i n 56 m i n u t e s and 72 m i n u t e s r e s p e c t i v e l y , w i t h no change i n the c o u r s e o r i n t h e p o s t mortem appearance o f the The b l o o d p r e s s u r e f e l l ,  after  intestines.  l i g a t i o n , t o a l e v e l o f between  - 40 80-90 mm. Hg o v e r t e n m i n u t e s , and t h e n d e c l i n e d s l o w l y u n t i l a p r e s s u r e o f 30-40 mm. Hg was r e a c h e d .  I n the t h i r d and f o u r t h e x p e r i m e n t s ,  d e c r e a s e i n c i r c u l a t i n g b l o o d volume was measured a f t e r l i g a t i o n , b u t w i t h t h e s p l e e n removed ( T a b l e V I I I ) .  portal vein  B o t h t h e s e dogs  showed a g r e a t e r degree o f e x t r a v a s a t i o n o f b l o o d i n t o t h e than those without splenectomy.  the  mesentery  However, t h e i r course was u n i n f l u e n c e d ,  and t h e d e c r e a s e i n c i r c u l a t i n g b l o o d volume was w i t h i n the range o f t h o s e dogs w i t h o u t s p l e n e c t o m y .  In effect,  the s p l a n c h n i c v a s c u l a r bed  seems t o have a huge c a p a c i t y f o r d i s t e n s i o n , and t h i s i s n o t d i m i n i s h e d n o t a b l y b y splenectomy.  The c a p a c i t y o f the s p l e e n i n dogs has n o t been  recorded.  T h i s i n d i c a t e s t h a t whatever t h e e f f e c t  o f sodium p e n t o b a r b i t a l  i s on t h e s p l e e n , i t has l i t t l e i n f l u e n c e on the c o u r s e o f e v e n t s ,  for  t h e r e can be no g r e a t e r s t i m u l u s t o s p l e n i c enlargement t h a n a r i s e i n p o r t a l venous p r e s s u r e ,  n o r d e c r e a s e i n the s p l e n i c volume t h a n t o t a l  removal.  The e f f e c t o f p e n t o b a r b i t a l a n a e s t h e s i a c r i t s i s harder t o evaluate.  The g e n e r a l e f f e c t  on p e r i p h e r a l  haemato-  i s t o produce an immediate  h a e m o d i l u t i o n w h i c h c o n t i n u e s unchanged f o r s e v e r a l hours ( B o l l m a n e t 1938, W i g g e r s 1942, C o u r t i c e and Gunton 1 9 4 9 ) .  I f however t h e  al  experiments  c o n t i n u e f o r t o o l o n g , h a e m o c o n c e n t r a t i o n w i l l o c c u r , due t o d e h y d r a t i o n o f the a n i m a l ( S e a v e r s and P r i c e 1 9 4 9 ) .  I f haemorrhage o c c u r s ,  d i l u t i o n i s p r e v e n t e d , f o r dogs under p e n t o b a r b i t a l a n a e s t h e s i a no p a r t o f t h e plasma l o s t b y haemorrhage,  haemorestore  p r o b a b l y because o f a r t e r i o l a r  r e l a x a t i o n which prevents l o w e r i n g of c a p i l l a r y p r e s s u r e ,  and r e a b s o r p t i o n  - 41 from t h e t i s s u e s .  ( C o u r t i c e and Gunton 1949)  The r o l e o f t h e  as a b l o o d s t o r a g e depot f o r r e d c e l l s t o be m o b i l i z e d a f t e r  spleen haemorrhage  i s now u s u a l l y d i s c o u n t e d ( C o u r t i c e and Gunton 1949, G i b s o n e t a l . 1946, Delorme e t a l . 1 9 5 2 ) . F u r t h e r , h a e m a t o c r i t v a l u e s a r e known t o v a r y w i d e l y w i t h source of the b l o o d used.  the  F o r t h i s r e a s o n , l i t t l e i n f o r m a t i o n can be  o b t a i n e d from t h e f a l l o f h a e m a t o c r i t v a l u e s r e c o r d e d h e r e , b u t a p o s s i b l e e x p l a n a t i o n may l i e i n t h e r e t u r n t o t h e c i r c u l a t i o n o f plasma from t h e i n t e s t i n e s t h r o u g h the l y m p h a t i c s y s t e m .  5. S i t u a t i o n o f P o r t o - s y s t e m i c venous  anastomoses.  A l l specimens had w e l l i n j e c t e d p o r t a l Dog N o . 1  Weight 9 . 1 k g .  tributaries.  Male  The s u p e r i o r r e c t a l v e i n was f o l l o w e d down t h r o u g h t h e muscle l a y e r t o i t s t e r m i n a t i o n , a s h o r t d i s t a n c e from the a n u s . p e l v i c systemic veins contained l a t e x .  No  The p o s t e r i o r abdominal  w a l l had a s i n g l e , t h r e a d - l i k e v e i n c o n t a i n i n g l a t e x , w h i c h r a n from t h e mesentery t o the f a s c i a o v e r l y i n g the k i d n e y .  From  t h e c a r d i a , s m a l l v e i n s f i l l e d w i t h l a t e x d r a i n e d i n t o two main b r a n c h e s w h i c h r a n w i t h the two v a g i n e r v e s , and d r a i n e d i n t o t h e s y s t e m i c v e i n s on the p o s t e r i o r w a l l o f the t h o r a x .  No  o t h e r p o r t o - s y s t e m i c anastomoses c o u l d be f o u n d . Dog N o . 2  Weight 1 5 . 9 k g .  Male  A s m a l l b r a n c h r a n a n t e r i o r l y from t h e r e c t u m i n the r e f l e c t i o n o f p e r i t o n e u m onto the p o s t e r i o r s u r f a c e o f t h e p r o s t a t e , and t h e n c e i n t o a v e i n w h i c h d r a i n e d the r i g h t u r e t e r  \  - 42 and p o s t e r i o r a b d o m i n a l w a l l .  A few t i n y v e n u l e s c o u l d be seen  r u n n i n g i n t h e mesentery o f the r e c t u m , b u t no o t h e r v e i n s f i l l e d on the p o s t e r i o r abdominal w a l l .  From t h e mesentery o f  t h e duodenum, s m a l l branches f i l l e d w i t h l a t e x formed a v e i n ( 0 . 5 mm. d i a m e t e r ) w h i c h j o i n e d a lumbophrenic v e i n m e d i a l t o the l e f t s u p r a r e n a l v e i n , which then d r a i n e d i n t o the i n f e r i o r v e n a c a v a 1 cm. above t h e r i g h t r e n a l v e i n .  A t the  cardia,  s m a l l g a s t r i c branches amalgamated t o form main branches w h i c h accompanied the two vagus n e r v e s .  From t h e s e , t h r e e  b r a n c h e s r a n t o the p o s t e r i o r t h o r a c i c w a l l v e i n s , d r a i n i n g the l o w e s t 5 cm. o f the oesophagus. Dog N o . 3  Weight 1 5 . 0 k g .  (See F i g u r e  Male  Three cms. from the anus on t h e l e f t s i d e , a l a t e x f i l l e d  vein  ( 0 . 4 mm. d i a m e t e r ) r a n p o s t e r o l a t e r a l l y t o j o i n a v e i n on t h e s i d e w a l l o f the p e l v i s ( 0 . 8 mm. d i a m e t e r ) .  From the  anterior  a s p e c t o f t h e r e c t u m , a l a t e x f i l l e d v e i n r a n i n the  peritoneal  r e f l e c t i o n t o t h e p o s t e r i o r a s p e c t o f the p r o s t a t e .  This vein  was j o i n e d b y a s m a l l v e i n i n t h e m e s e n t e r y .  upper  A t the  r e c t u m t h r e e s m a l l v e i n s ( 0 . 3 mm. o r l e s s i n d i a m e t e r ) r a n from t h e r e c t a l network o f v e s s e l s t o the p o s t e r i o r abdominal w a l l . Two minute v e i n s r a n from the d u o d e n a l mesentery t o j o i n  the  l e f t l u m b o - a d r e n a l v e i n , b u t t h i s v e i n had o n l y t r a c e s o f latex within i t .  A l o n g t h e r i g h t "vagus a v e i n r a n c o n n e c t i n g  t h e v e i n s o f the c a r d i a w i t h t h o s e o f t h e l o w e r oesophagus o f t h e p o s t e r i o r t h o r a c i c w a l l i n a l a d d e r manner.  and  A l o n g the  l e f t v a g u s , a v e i n r a n c o n n e c t i n g w i t h t h e l o w e r oesophageal  -  43  -  v e i n s , b u t n o t anastomosing w i t h the v e i n s o f t h e thoracic w a l l . Dogs N o . 4  &  posterior  (See F i g u r e V b )  A t t e m p t s t o d i s p l a y anastomoses b y u s i n g r a d i o - o p a q u e  media  5  failed,  o n l y t h e m a i n p o r t a l venous t r i b u t a r i e s  filling.  Discussion: These d i s s e c t i o n s , i n w h i c h good f i l l i n g o f the s m a l l e s t was o b t a i n e d , show t h a t i n the d o g , the main p o r t o - s y s t e m i c anastomoses o c c u r a t t h e l o w e r end o f t h e oesophagus,  venules  venous  connecting  the  g a s t r i c p o r t a l v e i n s t o t h e oesophageal s y s t e m i c v e i n s , i n r e l a t i o n t o r i g h t and l e f t vagus n e r v e s .  Two o t h e r groups o f anastomoses o c c u r ,  o f a r e l a t i v e l y m i n o r d e g r e e , t h o s e i n the mesentery r u n n i n g t o the  the  but left  l u m b o - a d r e n a l v e i n , and t h o s e c o n n e c t i n g t h e l o w e r r e c t u m w i t h the prostatic veins.  These f i n d i n g s a r e s u p p o r t e d b y t h e c o u n t i n g r a t e s  o b r a i n e d i n the p o r t a l venous b l o o d when the l o w e r oesophagus and i t s v e i n s a r e o c c l u d e d (see T a b l e I I I ) .  W i t h o u t o c c l u s i o n , t h e p o r t a l venous  count r i s e s t o a much g r e a t e r e x t e n t on i n j e c t i o n o f P 5 2 l a b e l l e d r e d c e l l s i n t o a s y s t e m i c v e i n , t h a n when t h e oesophagus i s l i g a t e d . latter  I n the  case t h e r i s e can be a c c o u n t e d f o r b y the l e a k o f plasma i n t o  the bowel.  T h i s a l l o w s , a v e r y s m a l l i n f l o w from the s y s t e m i c c i r c u l a t i o n  t o the p o r t a l v a s c u l a r b e d . L i t t l e work has been done on p o r t o s y s t e m i c venous anastomoses save i n man.  Butler  (1S51)  i n an i n v e s t i g a t i o n o f t h e v e i n s o f the  oesophagus i n man drew a t t e n t i o n t o s i m i l a r venae c o m i t a n t e s o f the  vagus  n e r v e , j o i n i n g t h e l e f t g a s t r i c v e i n s t o t h e azygos v e i n s , i n a d d i t i o n t o s u b e p i t h e l i a l and submucous  networks.  - 44 Wermuth (1939) i n v e s t i g a t i n g t h e anastomoses a t t h e o t h e r end o f t h e g a s t r o - i n t e s t i n a l t r a c t , u s i n g l a t e x i n j e c t i o n s , remarked on two main groups a ) l a t e r o c r a n i a l , from r e c t u m t o an h y p o g a s t r i c v e i n on e i t h e r  side,  b ) d o r s o v e n t r a l , from the rectum a t a l o w e r l e v e l t h a n a ) t o the  side  of the uterus* Edwards (1951) b y u s i n g a b a r i u m s u l p h a t e femoral v e i n s i n three normal s u b j e c t s , Schmiedel  (1744);  suspension i n j e c t e d i n t o  confirmed a d e s c r i p t i o n by  namely, t h a t two main groups  occurred.  1) Normal m u l t i p l e f i n e v e s s e l s above t h e rectum and i n the a r e a s o f the  the  retroperitoneal  abdomen  2) Abnormal communications between t h e p o r t a l and s y s t e m i c systems,  e.g.  t e r m i n a t i o n o f t h e p o r t a l v e i n i n the i n f e r i o r vena c a v a . I n h i s a r t i c l e t h e r e a r e no c l e a r - c u t d e s c r i p t i o n s o f t h e n o r m a l v e s s e l s . I n the p r e s e n c e o f p o r t a l h y p e r t e n s i o n ,  there are  a r t i c l e s concerning the s i t u a t i o n of d i l a t e d portosystemic  numerous anastomotic  and c o l l a t e r a l v e i n s (Sappey 1883, Hclndoe 1928) w h i c h a l s o d e v e l o p i n the dog when p a r t i a l o b s t r u c t i o n o f the p o r t a l v e i n i s done.  C h i l d et a l .  (1951) remarked on t h e w e l l marked p e l v i c p o r t o s y s t e m i c c o l l a t e r a l s i n the Macaca M u l l a t a monkey, whose venous p a t t e r n i s s a i d t o resemble  that  o f man. 6.  E x h i b i t i o n of a n t i b i o t i c s S i x e x p e r i m e n t s were p e r f o r m e d ,  i n t h r e e o f which the  antibiotic  was g i v e n p r i o r t o l i g a t i o n o f t h e p o r t a l v e i n , i n t h r e e f o l l o w i n g l i g a t i o n . The method o f l i g a t i r f g the p o r t a l v e i n d i d not d i f f e r from t h a t p r e v i o u s l y described.  C o n t i n u o u s r e c o r d s o f s y s t e m i c a r t e r i a l b l o o d p r e s s u r e were  45  -  obtained.  -  C r y s t a l l i n e p e n i c i l l i n G was g i v e n i n t r a v e n o u s l y i n t o a f e m o r a l  v e i n j t h e a u r e o m y c i n was g i v e n b y mouth b y hand f e e d i n g .  No b a c t e r i o l o g i c a l  s t u d i e s were done w i t h t h e s e a n i m a l s . (a)  A n t i b i o t i c g i v e n p r i o r to (i)  Female.  ligation  Weight 2 5 . 0 k g .  500,000 u n i t s o f p e n i c i l l i n  1 hour p r i o r t o l i g a t i o n .  Dog d i e d 50 m i n u t e s f o l l o w i n g  l i g a t i o n , without a l t e r a t i o n i n i t s (ii)  Male.  Weight 7 . 5 k g .  given  course.  500,000 u n i t s o f p e n i c i l l i n g i v e n  6§- h o u r s , 3 § hours and h a l f an h o u r b e f o r e l i g a t i o n .  Death i n  65 m i n u t e s f o l l o w i n g l i g a t i o n , c o u r s e u n a l t e r e d . ( i i i ) Female.  Weight 2 3 . 2 k g .  250 mgm. aureomycin g i v e n i n t h r e e  doses (10 a . m . , 1 p . m . and 4 p . m . ) on day b e f o r e , t h r e e doses (8 a . m . , 11 a . m . and 2 p . m . ) on day o f l i g a t i o n .  The p o r t a l  v e i n was l i g a t e d 49 m i n u t e s a f t e r  The dog d i e d  the l a s t d o s e .  73 m i n u t e s l a t e r , w i t h u n a l t e r e d c o u r s e . (b)  A n t i b i o t i c given after (i)  Male.  Weight 2 0 . 4 k g .  after l i g a t i o n . (ii)  Male.  500,000 u n i t s o f p e n i c i l l i n 9 m i n u t e s  Death i n 32 m i n u t e s , c o u r s e u n a l t e r e d .  Weight 1 2 . 2 k g .  after l i g a t i o n .  500,000 u n i t s o f p e n i c i l l i n 10 m i n u t e s  D e a t h i n 100 m i n u t e s , c o u r s e u n a l t e r e d .  Weight 1 5 . 9 k g .  after l i g a t i o n . ( i i i ) Male.  ligation  500,000 u n i t s o f p e n i c i l l i n 5 m i n u t e s  D i e d i n 114 m i n u t e s .  Course u n a l t e r e d .  Discussion: F o l l o w i n g the o b s e r v a t i o n s o f M a r k o w i t z e t a l . ( I S 4 9 ) on t h e a b i l i t y of p e n i c i l l i n to p r o t e c t a g a i n s t the e f f e c t o f h e p a t i c l i g a t i o n , t h e s e e x p e r i m e n t s were c a r r i e d o u t .  artery  I n t h i s s m a l l number,  the  - 46 e x h i b i t i o n o f a n t i b i o t i c s had no e f f e c t whatsoever on the outcome o f l i g a t i o n o f t h e p o r t a l v e i n , whether g i v e n b e f o r e o r a f t e r  ligation.  It  was thought t h a t perhaps t h e a n t i b i o t i c s i n q u e s t i o n m i g h t be u n a v a i l i n g a g a i n s t t h e organisms and t h a t f u r t h e r work s h o u l d be done t o  investigate  t h e n o r m a l b a c t e r i a l f l o r a o f t h e d o g ' s l i v e r , and t h e i r s e n s i t i v i t y t o antibiotics.  T h i s work has n o t been c o m p l e t e d .  GENERAL DISCUSSION These e x p e r i m e n t s have shown t h a t t h e average r e d u c t i o n i n c i r c u l a t i n g b l o o d volume a f t e r  l i g a t i o n o f the p o r t a l v e i n i s 51.3%  (18.77) of the p r e l i g a t i o n volume.  T h i s f i g u r e i s higher than that of  M a l l e t - G u y e t a l . ( 1 9 5 0 ) , b u t i f comparable volumes a r e t a k e n , t h a t i s , i f t h e b l o o d n o r m a l l y p r e s e n t w i t h i n the s p l a n c h n i c c i r c u l a t i o n i s s u b t r a c t e d from t h e volume s e q u e s t r a t e d a f t e r figure,  l i g a t i o n , then the  resulting  4 4 . 8 $ , i s midway between t h a t o f Elman a n d C o l e and t h a t o f  Boyce e t a l .  E f f o r t s t o determine  the volume o f b l o o d w h i c h i s r e q u i r e d t o be  b l e d t o produce f a t a l l e v e l s o f shock have been abandoned,  f o r the  response  o f the dogs i s so v a r i a b l e t h a t no f i g u r e i s u s e f u l ( H u i z e n g a e t a l . 1 9 4 3 ) . V a r i o u s e s t i m a t i o n s have been g i v e n i n the p a s t (see T a b l e I X a ) .  These  have l i t t l e comparable v a l u e f o r the method o f d e t e r m i n i n g them was so variable.  Of much more v a l u e a r e t h e f i g u r e s o b t a i n e d b y b l e e d i n g t o  a r b i t r a r y l e v e l s o f i r r e v e r s i b l e shock ( see T a b l e I X b ) .  Again,  i s d i f f i c u l t f o r t h e l e v e l s o f shock b l o o d p r e s s u r e d i f f e r e d . t h e p r o c e d u r e o f Wiggers e t a l . (1946) was u s e d .  In  comparison general  I n t h i s , bleeding (at a  r a t e o f around 40 m l / k i l o body w e i g h t / m i n ) c o n t i n u e d u n t i l the b l o o d  - 47 p r e s s u r e f e l l t o a l e v e l o f 50 mm. H g . , a t w h i c h l e v e l i t was m a i n t a i n e d for  90 m i n u t e s , when f u r t h e r b l e e d i n g was performed t o reduce the b l o o d  p r e s s u r e t o 30 mm. H g . f o r 45 m i n u t e s more. to the  r e s u l t s o f the p r e s e n t e x p e r i m e n t s  the l a t t e r  are g e n e r a l l y h i g h e r .  I f t h e s e amounts a r e  ( 4 3 . 1 - 7 3 . 2 m l / k g , average  The t i m e s o f s u r v i v a l a r e however  The d e t e r m i n a t i o n s were made 30 - 40 m i n u t e s a f t e r oundoubtedly f u r t h e r  shorter.  o c c l u s i o n , and  T h e r e f o r e an adequate e x p l a n a t i o n o f the cause of  l i g a t i o n may l i e i n the decrease o f the c i r c u l a t i n g b l o o d  volume t o a l e v e l i n c o m p a t i b l e w i t h an adequate c a r d i a c o u t p u t t o life.  57.9),  d e c r e a s e i n the c i r c u l a t i n g b l o o d volume must have  occurred before death. death a f t e r  compared  sustain  However, the i n e v i t a b i l i t y o f d e a t h a f t e r - p o r t a l v e i n o c c l u s i o n  c o n t r a s t e d w i t h t h e o c c a s i o n a l s u r v i v a l a f t e r b l e e d i n g t o s u c h l e v e l s , and t h e f a c t t h a t t h e t o t a l v a s c u l a r b e d has been r e d u c e d b y t h e e x c l u s i o n o f t h e s p l a n c h n i c p o r t i o n ( 1 7 . 7 m l / k g ) so t h a t the s m a l l e r c i r c u l a t i n g b l o o d volume i s r e q u i r e d t o s e r v e a s m a l l e r v a s c u l a r a r e a suggest t h a t  other  f a c t o r s are i m p l i c a t e d .  An a n a l o g y may make t h i s c l e a r .  I f b o t h l e g s are amputated,  the  c o n t a i n e d b l o o d , w h i c h may amount t o 16% o f the t o t a l c i r c u l a t i n g b l o o d volume, i s removed from the c i r c u l a t i o n .  I f the o r i g i n a l b l o o d volume was  1,000 m l . , t h e n t h e new b l o o d volume i s 840 m l .  B u t t h i s volume i s  r e q u i r e d t o s e r v e a v a s c u l a r bed w h i c h has been r e d u c e d b y 160 m l . T h e r e f o r e t h e r a t i o o f c i r c u l a t i n g b l o o d t o v a s c u l a r bed has n o t been altered.  I f now b l e e d i n g o c c u r s , and t h e c i r c u l a t i n g b l o o d volume i s  found t o be 500 m l , , t h e n the r e d u c t i o n i n c i r c u l a t i n g b l o o d volume i s n o t 50%, b u t t h e d i f f e r e n c e between t h e p o s t b l e e d i n g b l o o d v o l u m e , and the p o s t a m p u t a t i o n b l o o d v o l u m e , namely 340 m l , , o r e x p r e s s e d as a  - 48 percentage  340 840  x  l  Q  Q  m  40.5$.  I f t h e s p l a n c h n i c v i s c e r a a r e c o n s i d e r e d t o be the  amputated  l e g s , and t h e l o s s o f b l o o d i n t o the s p l a n c h n i c bed t o be the  post  amputation b l e e d i n g , then the t r u e r e d u c t i o n i n c i r c u l a t i n g b l o o d volume, t a k i n g t h e d o g ' s w e i g h t t o be 10 k g . , can be worked o u t . P r e l i g a t i o n b l o o d volume  769 m l .  =  Volume o f b l o o d c o n t a i n e d w i t h i n the s p l a n c h n i c v i s c e r a  177  m  m  i  >  . * . C a p a c i t y of reduced v a s c u l a r area =  592 m l .  P o s t l i g a t i o n c i r c u l a t i n g b l o o d volume •  327 m l .  .  . True r e d u c t i o n i s 592 m l . - 327 m l . ; o r 265 m l . , o r e x p r e s s e d as a %  265  -,  n n  44.8$  m  592  T h i s must be a s s o c i a t e d w i t h t h e reduced p o r t a l b l o o d s u p p l y t o the l i v e r .  T h i s may produce  t o the l i v e r ,  ( i i ) a d e c r e a s e i n some p a r t i c u l a r component s u p p l i e d  by the p o r t a l b l o o d ,  ( i ) a d e c r e a s e i n t h e oxygen s u p p l y  ( i i i ) a t o x i n produced i n t h e congested b o w e l .  E f f o r t s t o i m p l i c a t e a t o x i n have g e n e r a l l y f a i l e d ; t h i s does n o t n e c e s s a r i l y e x c l u d e such a t o x i n . on p o r t a l venous b l o o d . detectable difference  L i v e r r e g e n e r a t i o n i s n o t dependent  Dogs w i t h E c k f i s t u l a e s u r v i v e w i t h o u t  i n b i o c h e m i s t r y , or i n t h e i r g e n e r a l  However, i n s u c h dogs, any p o r t a l component can r e a c h t h e eventually  by the  hepatic artery;  health. liver  a g a i n such a p o s s i b i l i t y  - 49' cannot be e x c l u d e d . L i v e r h y p o x i a i s known t o o c c u r i n shock ( E n g e l e t a l . 1943, 1944).  S u r v i v a l o f dogs f o l l o w i n g b l e e d i n g t o o t h e r w i s e  irreversible  shock l e v e l s can be o b t a i n e d i f the oxygen s u p p l y t o the l i v e r supplemented  ( F r a n k e t a l . 1946, Delorme 1 9 5 1 ) .  is  L i g a t i o n of the  portal  v e i n w i l l cause h y p o x i a o f the l i v e r b y d e p r i v i n g the l i v e r o f t h e oxygen c a r r i e d b y the p o r t a l venous b l o o d .  Though t h e h e p a t i c a r t e r y i s  the  dominant s o u r c e o f oxygen ( B a r c r o f t and Shore 1912, B l a l o c k and Mason 1 9 3 6 ) , the p o r t a l venous b l o o d does s u p p l y a s u b s t a n t i a l  portion of  the  oxygen r e q u i r e d (Smythe e t a l . 1 9 5 1 ) . On r e d u c t i o n o f the p o r t a l v e i n f l o w , rises  the h e p a t i c a r t e r y f l o w  (Schwiegk 1932, G r i n d l a y e t a l . 1941, S a n c e t t a 1 9 5 3 ) ,  i n c r e a s i n g t h e t o t a l oxygen s u p p l i e d b y t h i s s o u r c e .  thereby  T h i s would compensate  i f t h e h e p a t i c a r t e r y s u p p l y d i d n o t i t s e l f d e c l i n e due t o the d e c l i n e i n cardiac  output. I f l i g a t i o n i s i n c o m p l e t e , when the c i r c u l a t i n g b l o o d volume i s  augmented b y t h e escape o f p o r t a l b l o o d b a c k i n t o t h e s y s t e m i c c i r c u l a t i o n , o r i f t h e c i r c u l a t i n g b l o o d volume i s m a i n t a i n e d b y t r a n s f u s i o n ,  the  flow  w i t h i n the h e p a t i c a r t e r y i s p r o b a b l y m a i n t a i n e d and s u r v i v a l f o l l o w s . L i g a t i o n o f the a o r t a above t h e c o e l i a c a x i s , when combined w i t h l i g a t i o n o f t h e p o r t a l v e i n , postpones d e a t h and a l l o w s s u r v i v a l 4 hours (Elman and C o l e 1 9 3 4 ) .  L i g a t i o n of the splanchnic a r t e r i e s a f t e r p o r t a l v e i n  l i g a t i o n a l s o postpones d e a t h (Boyce e t a l . 1 9 3 5 ) .  Simultaneous l i g a t i o n  o f t h e h e p a t i c a r t e r y and p o r t a l v e i n has n o t been  investigated.  I n two dogs t h e r i g h t f e m o r a l a r t e r y was connected t o t h e  portal  v e i n on t h e h e p a t i c s i d e o f t h e l i g a t u r e , i n an a t t e m p t t o a u t o - v i v i perfuse in their  the l i v e r .  These dogs l i v e d 105 and 146 m i n u t e s , b u t no  course was s e e n .  alteration  However, t h i s i s i n c o n c l u s i v e , f o r i f the b l o o d  p r e s s u r e was m a i n t a i n e d , t h e r e w o u l d be a g r e a t e r escape o f b l o o d i n t o splanchnic bed.  the  T h i s v a s c u l a r bed w o u l d appear t o have an i n e x h a u s t i b l e  c a p a c i t y t o c o n t a i n b l o o d p u t i n t o i t b y the f e e d i n g  arteries.  There a r e no r e s u l t s a v a i l a b l e o f measurements o f t h e e x t e n t o f t h e h y p o x i a o f the l i v e r o r o f t h e amount o f t h e d e c r e a s e i n f l o w o f t h e hepatic artery following p o r t a l vein l i g a t i o n . these p o i n t s i s  Further investigation of  indicated.  The p r e l i m i n a r y e x p e r i m e n t s were made u s i n g i n t e r m i t t e n t  positive  p r e s s u r e o x y g e n a t i o n u s i n g a B u r n s ' v a l v e (Adelman, 1950); i n 4 dogs s u r v i v a l t i m e s were 5 0 , 7 0 , 56, and 86 m i n u t e s , average 6 5 . 5 m i n u t e s .  It  does n o t appear t h a t any advantage i s g a i n e d b y r e s p i r a t i o n o f pure o x y g e n . I n haemorrhagic  s h o c k , i f the p o r t a l venous p r e s s u r e i s r e d u c e d , t h e n a much  g r e a t e r d e c r e a s e o c c u r s i n the p o r t a l venous f l o w , t h a n i s the case w i t h a comparable f a l l i n s y s t e m i c a r t e r i a l p r e s s u r e and t h e h e p a t i c a r t e r i a l flcwQ (Wiggins e t a l . 1 9 4 6 ) .  T h i s was c o n f i r m e d b y S e l k u r t e t a l . (1947) who  measured the r e d u c t i o n i n p o r t a l venous f l o w a f t e r b l e e d i n g t o a l e v e l o f 40 mm. H g .  They f o u n d t h a t the prehaemorrhage f l o w o f 2 6 . 0 m l / m i n / k g body  w e i g h t was r e d u c e d t o 3 . 7 m l / m i n / k g .  N e v e r t h e l e s s , t h e r e appears t o be  a n a t t e m p t t o m a i n t a i n p o r t a l f l o w a t t h e expense o f the s u p p l y t o p o s t e r i o r h a l f o f t h e body ( B l a l o c k and L e v y 1 9 3 7 ) .  the  - 5i These o b s e r v a t i o n s do n o t e x p l a i n what d e l e t e r i o u s p r o c e s s f o l l o w s hypoxia o f the l i v e r .  Two hypotheses a r e p r o p o s e d p r e s e n t l y .  S h o r r e t a l . ( l ° 5 l ) have p o s t u l a t e d the o c c u r r e n c e o f a v a s o d e p r e s s o r m a t e r i a l , b e l i e v e d t o be i d e n t i c a l w i t h f e r r i t i n , w h i c h i s p r o d u c e d i n t h e h y p o x i c l i v e r , and w h i c h c a n be shown t o i n h i b i t the e f f e c t o f n e o s y n e p h r i n e on t h e meta a r t e r i o l e s o f t h e r a t m e s o - a p p e n d i x .  Frank et a l .  (1952) b y o b s e r v i n g the e f f e c t i v e n e s s o f a u r e o m y c i n i n i n c r e a s i n g t h e s u r v i v a l f o l l o w i n g haemorrhagic shock ( b l e e d i n g t o 30 mm. H g . ) p o s t u l a t e t h a t d e a t h from t r a u m a t i c shock i n w h i c h t h e b l o o d volume d e f i c i t had been c o r r e c t e d was due t o a t o x i n o f a n a e r o b i c b a c t e r i a l o r i g i n .  His  manner o f g i v i n g a u r e o m y c i n was t o a d m i n i s t e r 2.5 gm. t w i c e d a i l y u n t i l s t o o l c u l t u r e s were f r e e o f £ . c o l i and C l o s t r i d i a , w h i c h u s u a l l y t o o k 6 days.  Compared w i t h a c o n t r o l g r o u p , where a 12$ s u r v i v a l o c c u r r e d ,  68% s u r v i v e d w i t h t h i s d o s a g e .  I f 5 gms. were g i v e n , o n l y 3-5 hours  b e f o r e b l e e d i n g , h$% s u r v i v e d .  P e n i c i l l i n was u n a b l e t o i n f l u e n c e the  course o f events.  The o r g a n i s m r e s p o n s i b l e was n o t d i s c l o s e d .  B u t Hardy  e t a l . (195U) were u n a b l e t o s u b s t a n t i a t e t h e work o f F r a n k e t a l . , and N e l s o n (195U) found an i d e n t i c a l i n c i d e n c e o f p o s i t i v e b l o o d c u l t u r e s i n shocked dogs and i n c o n t r o l s .  The p r e s e n t e x p e r i m e n t s have n o t p r o p e r l y i n v e s t i g a t e d the effect of a n t i b i o t i c s .  A l l t h a t c a n be s a i d i s t h a t i n the doses g i v e n  the course i s not i n f l u e n c e d .  These e x p e r i m e n t s s h o u l d be f u r t h e r  pursued.  - 52 SUMMARY A review of the literature on ligation of the portal vein has been presented.  A brief survey of the literature on the ligation of the  hepatic veins and the hepatic artery has been included. The review reveals that while there i s no disagreement that the result of sudden acute ligation of the portal vein i n dogs i s inevitably death, there i s disagreement as to the cause of death.  The main theories are (i) that  exsanguination into the splanchnic vascular bed occurs, ( i i ) that the loss of blood i s insufficient to cause death, and that other factors must be implicated, the "toxic" theory.  The species difference i n the effects of  ligation appears to l i e i n the degree of porto-systemic venous anastomoses. The experiments described i n this thesis were performed with the dog as the experimental animal.  A measurement of the decrease i n circu-  lating blood volume following ligation of the portal vein, using the "labelled" red c e l l method, was made. With 11 dogs, 30 minutes after portal vein ligation, the decrease amounted to 57.9$ of the original blood volume.  It was concluded that this amount of blood loss was not adequate  to account for the inevitability of death, or the short period of survival (79.7 minutes) when compared to the effects of bleeding comparable quantities of blood, or bleeding to comparable levels of blood pressure. It was considered that valid consecutive estimations of blood volume could be made using the "labelled" red c e l l method. A measurement of the normal splanchnic vascular blood volume was made using 10 dogs. This amounted to 21.7$ of the circulating blood volume, or 17.7 ml. per kilogram body weight.  - 55: -  Haematocrit estimations were made on the systemic arterial blood and portal venous blood before and after ligation of the portal vein.  There was a significant decrease i n the systemic arterial  haematocrit, and rise i n the portal venous haematocrit. By the i n jection of latex into the portal vein of 3 dogs, the main portosystemic venous anastomoses were found to occur i n relation to the vagus nerves at the lower end of the oesophagus. Other porto-systemic venous anastomoses ware of minor importance. It was not possible to influence the outcome of acute portal vein ligation by splenectomy, or by antibiotics under the conditions of the experiments.  TABLE I S u r v i v a l Times ( m i n s . ) a f t e r O c c l u s i o n o f P o r t a l V e i n Dog No.  Oesophageal V e s s e l s Occluded  Dog No.  No Oesophageal Ligature  Dog No.  No Oesophageal L i g a t u r e H e p a r i n - 10 mgs/kg  26 27  124 90  1 2  75 59  12 13  50 70  3  46  14  56  28  93  4  54  15  85  29  61  5  53  16  95  30  110  6  52  17  89  31  55  7  58  18  95  32  67  8  61  19  77  33  102  9  48  20  47  34  95  10  63  21  74  11  47  22  95  23  85  24  85  25  113  Average w i t h calculated standard d e v i a t i o n .  56.0  +8.5  79.7 * 18.9  8 8 . 6 t 23.26  TABLE II Reduction i n C i r c u l a t i n g  Post-ligation circulating b l o o d volume (ml/kg) (ml)  Reduction of c i r c u l a t i n g b l o o d volume  Dog  Sex  Wt. (kg)  1  F  9.1  798  87.7  399  43.8  50.0  2  M  18.2  1452  79.8  826  45.5  43.1  3  F  4.5  347  77.1  113  25.1  67.4  4  M  10.0  797  79.7  356  35.6  55.3  5  M  14.1  1023  72.6  468  33.2  54.3  6  'M  10.0  675  67.5  181  18.1  73.2  7  F  15.1  1186  78.5  583  38.6  50.8  8  M  15.9  1076  67.1  424  26.7  60.3  9  M  17.3  1435  82.9  570  33.0  60.3  10  M  25.9  1930  74.5  914  35.3  52.6  11  F  10.0  788  78.8  244  24.4  69.0  13.6  1045  76.9+ 6.56  462  32.7* 8.23  57.9* 8.77  Average w i t h calculated standard deviation  Preligation circulating b l o o d volume (ml/kg) (ml)  B l o o d Volume  .TABLE  III  T r u e C o u n t i n g R a t e s i n C / S / l O m l . f o r S y s t e m i c and P o r t a l Venous Systems A f t e r I n j e c t i o n o f L a b e l l e d Red C e l l s Systemic Blood  P o r t a l Venous B l o o d  (7)  5 mins. a f t e r 2nd i n j e c t i o n (36-41 m i n s . a f t e r p . v . occlusion) (8)  156.6  115.1  153-8  98.2  241-7  72.5  125.0  73-4  101.3  1669.1  328.7  622.6  95.6  647-7  104.0  95.4  372.0  277.9  196.9  140-3  203-8  103-5  47.1  77-5  157.7  334.8  83-3  137.0  83-8  100.7  304-5  258.5  84.9  732.5  283.4  338.1  111.0  356.0  105-3  7  127-7  101.9  79.8  307.1  301.4  138.5  108-4  147.6  106.6  8  189-7  143-5  75 ;e  516.9  360.3  197-2  103-9  231.0  117.2  9  95.0  80.5  84-7  172.0  213-7  95.3  100-4  10  107.8  87-3  80.9  187-1  214-4  120.8  112.0  102.0  84-5  11  136.5  117.5  86.1  409-8  343.9  191-5  140.3  181.2  94.6  28-31 m i n s . after occlusion of p o r t a l vein (background) (2)  5 mins. after 2nd i n j e c t i o n (36-41 m i n s . a f t e r p.v.occlusion) (4)  (5)  28-31 m i n s . after occlusion of p o r t a l v e i n (background) (6)  293-9  222.1  92.4  101.4  507-8  77.9  140.4  133.9  5  60.8  6  %  column 2 i s o f column 1 (3)  Pog  5 mins. a f t e r 1st i n j e c t i o n (1)  1  136.0  132.3  97.3  2  58.0  42.0  3  651.1  4  Average w i t h calculated standard deviation.  85-0 + 13.8  %  column 4 i s o f column 2  278.8 + 8 0 . 2  %  column 6 i s o f column 1  117.2 + 15-9  *  column 8 i s o f column 6  (9)  93-3  97.9  101.3  +.7.5  TABLE IV Estimation of blood volume of dogs, various authors. Method  Volume (ml/kg body weight)  Bonnycastle & Cleghorn (1942)  T-1824  82.7  Courtice (1943)  T-1824  79.0  Krieger e t a l . (1948)  T-1824  105.0  Iodinated protein  94.0  Author  P Delorme et a l . (1951) HcLain et a l . (1951)  P  3 2  32  97.0 100.3  Bleeding  62.0  T-1824  89.0  TABLE V C o n s e c u t i v e e s t i m a t i o n s o f b l o o d volume  Sex  Wt. (kg)  1 s t B l o o d Volume determination, (ml,)  2nd B l o o d Volume determination (ml.)  Dog 1.  Male  18.8  1338.0  1380.0  Dog 2 .  Female  6.8  466.0  452.3  3 r d B l o o d Volume determination (ml.) 1412.3  ,  i  TABLE V I  Dog N o .  Wt. (kg) Sex  Measurement o f S p l a n c h n i c V a s c u l a r B l o o d Volume Splanchnic Circulating ml/kg B l o o d Volume ( m l ) B l o o d Volume ( m l )  ml/kg  % of Circulating B l o o d Volume  1  5.9  F  393.5  66.7  60.3  10.2  15.3  2  6.6  F  650.8  98.6  99.0  15.0  15.2  3  4.1  F  472.4  115.2  96.3  23.5  20.4  4  5.7  M  337.8  59.3  56.8  10.0  16.8  5  7.3  F  513.9  70.4  103.8  14.2  20.2  6  15.5  F  1299.7  83.9  297.7  19.2  22.9  7  6.8  F  612.8  90.1.  186.3  27.4  30.4  8  17.1  M  1514.7  88.6  377.1  22.1  24.9  9  18.6  M  1233.5  66.3  253.1  13.6  20.5  10  9.6  M  692.4  72.1  210.0  21.9  30.3  772.2  81.4117.4  174.0  17.7:  21.7*5.5  Average  9.7 with calculated standard d e v i a t i o n .  TABLE VII Haematocrits Following occlusion of portal vein Preanaesthetic Venous Dog Systemic (1) (2) 1 2 3 4 5 6 7 8 9 10 11  40 43 46 28 40 57 55 52 46 47 43  Postanaesthetic Arterial Systemic (3) 34 41 45 30 40 56 53 50 44 46 43  Difference (3) - (2) (4)  Deviation From Mean (5)  36 34 45 29 35 55 47 43 40 40 43  4.6 0.6 0.4 3.4 1.4 0.4 0.6 0.6 0.6 0.4 1.4  -6 -2 -1 •2 0 -1 -2 -2 -2 -1 0  Deviation From Mean (8) 5-2 3.8 3.2 2.2 1.8 2.2 2.8 3.8 0.8 2.8 3-2  +2 -7 0 -1 -5 -1 -6 -7 -4 -6 0  After 36-41 mins. Arterial Systemic (9)  After 28-31 mins. Portal Difference Deviation Venous (10) - (3) From Mean (12) (10) (11) 60 66 75 48 62 73 72 75 66 65 61  26 21 30 18 22 17 19 25 22 19 18  Mean -3.2  Mean -1.4 Standard deviation - /6(x - x ) n -1  2  Standard deviation 1  n -1  - /100.04 10  -  -  1.96  a  1 0  6  Standard deviation - / S ( x - x V n -1 170.75 10  3.16  Standard error of mean « 0.301 t = 5^2 . 07301 .' P<0.01  4-5 0.5 8.5 3- 5 0.5 4- 5 2.5 4-5 0.5 2.5 3.5  Mean 21.5  - / 38.56 10  Standard error of mean - 0.59 t = 1^4 • 2.3 3759 p < 0.05  After 28-31 mins. Difference Arterial (6) - (3) Systemic (6) (7)  4.13 Standard error of mean - 1.26 t - . * \ - 17.0 21  /. p < 0.01  After 36-41 mins. Portal Venous (13)  TABLE F i l l Reduction i n c i r c u l a t i n g blood volume following splenectomy and p o r t a l v e i n l i g a t i o n  Dog  Sex  Weight kg  Blood Volume ml ml/kg  1  M  20.9  1893  M  14.1  874  90.5 62.0  Blood volume following splenectomy and p o r t a l vein l i g a t i o n nil  % reduction  S u r v i v a l time mins.  754.7  60.1  68  471.0  46.1  72  TABLE IX Volume o f b l o o d removed t o cause " i r r e v e r s i b l e '  1  shock  (a) B y b l e e d i n g d e f i n i t e volumes o f b l o o d  (b) B y b l e e d i n g t o a r b i t r a r y " i r r e v e r s i b l e " shock l e v e l s  Author  Author  Amount ml/kg  Range  Average  ml/kg  ml/kg  20-56  40.0  B l a l o c k (1931)  45  H u i z e n g a (1943)  Boyce (1935)  58  Ingraham (1950)  I r e n e u s (1944)  50  Hay (1951)  27.5-67.2  42.9  M a l l e t - G u y (1950)  40  Wang (1952) N e l s o n (1954)  48.8-71.5  60.8 52.0  49.9 ° i  Fig.  I  Concurrent recordings of p o r t a l v e i n b l o o d pressure and s y s t e m i c b l o o d p r e s s u r e .  Fig. Mixing of P  5 2  II  l a b e l l e d r e d c e l l s i n the g e n e r a l  Mixing of P^  2  labelled red c e l l s  circulation.  i n the general c i r c u l a t i o n .  40  Corrected counts/  20 Dog I  -*  6  2  4  6  8  10  20 Tlas (alrmtee)  30  40  Dog I I .  Fig. I l l M i x i n g o f P32 l a b e l l e d r e d c e l l s i n the g e n e r a l c i r c u l a t i o n . Continuous r e c o r d o f c o u n t i n g r a t e s .  Standard e r r o r _ 5$ accuracy F u l l s c a l e meter range "  -fe- •  5,000  Standard e r r o r „ accuracy counts/min.  2%  Fig.  IV (a)  Mixing o f P™ l a b e l l e d red c e l l s i n general 30 m i n s . a f t e r p o r t a l v e i n l i g a t i o n . Mixing of P-_ labelled red cells following 30 Bias, after  circulation  portal TO In ligation.  Dog I.  -Ma 10  15  F i g . IV (b) Mixing o f P32 l a b e l l e d red c e l l s i n general c i r c u l a t i o n 30 m i n s . f o l l o w i n g l i g a t i o n o f p o r t a l v e i n . .Continuous r e c o r d o f counting r a t e s  -  68  -  F i g . V (a) Dog. 2.  P o r t a l venous t r i b u t a r i e s i n j e c t e d w i t h l a t e x . M a i n a n a s t o m o t i c v e i n accompanying L . vagus n e r v e  S m a l l v e n u l e r u n n i n g i n mesentery o f duodenum  - 69  -  F i g . V (b) Dog 3.  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