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. 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 . Two small venules running i n mesentery of large bowel. Small venule running from l e f t side of rectum to j o i n systemic v e i n i n side w a l l of p e l v i s . \ R E F E R E N C E S 1. Adams, R . C . 2. Adelman, M . H . , Megibow, S . J . & B l u m , L . A Method o f A u t o m a t i c C o n t r o l l e d R e s p i r a t i o n f o r Anaesthesia i n the Dog. S u r g e r y - 28 s 101*0, December 1900. 3. Andrews, E . & H r d i n a , L . 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Acute ligation of the portal vein Johnstone, Frederick Robert Carlyle 1954
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