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Acute ligation of the portal vein 1954

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ACUTE LIGATION OF THE PORTAL VEIN by FREDERICK ROBERT CARLYLE JOHNSTONE A THESIS SUBMITTED IN PARTIAL FULFILMENT OF THE REQUIREMENTS FOR THE DEGREE OF MASTER OF SCIENCE i n the Department o f ANATOMY We accep t t h i s t h e s i s as conforming t o the s tandard r e q u i r e d from candida tes 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 I l l A B S T R A C T A r ev iew o f the l i t e r a t u r e on l i g a t i o n o f the p o r t a l v e i n has been p resen ted . A b r i e f survey o f the l i t e r a t u r e on the l i g a t i o n of the hepa t i c v e i n s and the h e p a t i c a r t e r y has been i n c l u d e d . The rev iew r e v e a l s t h a t w h i l e the re i s no disagreement t h a t the r e s u l t of sudden acute 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 dea th , there i s d i s - agreement as t o the cause o f dea th . The main t h e o r i e s are ( i ) t h a t exsangu ina t ion i n t o the sp l a nc hn i c v a s c u l a r bed o c c u r s , ( i i ) t h a t the l o s s o f b l o o d i s i n s u f f i c i e n t t o cause dea th , and t h a t o the r f a c t o r s must be i m p l i c a t e d , the " t o x i c " t h e o r y . The spec ies d i f f e r e n c e i n the e f f e c t s o f l i g a t i o n appears to l i e i n the degree o f po r to - sys t emic venous anastomoses. The experiments 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 the dog as the expe r imen ta l a n i m a l . A measurement o f t h e decrease 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 of the p o r t a l v e i n , u s i n g the " l a b e l l e d " r e d c e l l method, was made. I t was cons ide red t ha t v a l i d consecu t ive e s t i m a t i o n s of 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 " r e d c e l l method. Wi th 11 dogs, 30 minutes a f t e r p o r t a l v e i n l i g a t i o n , the decrease amounted to 51.9% o f the o r i g i n a l b l o o d volume. The measurement o f the normal sp l anchn ic 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 to 21,1% o f the c i r c u l a t i n g b lood volume, o r 17 .7 m l . per 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 sp l anchn 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 lood volume was r e q u i r e d t o serve a s m a l l e r v a s c u l a r a r e a , and i t was cons ide red t ha t the t r u e decrease i n c i r c u l a t i n g b lood volume was t he r e fo re 4 4 . 8 $ . I t was cons ide red t ha t t h i s amount o f b l o o d l o s s was not 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 in the systemic arterial haematocrit, and rise in 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 in relation to the vagus nerves at the lower end of the oesophagus. Other porto-systemic venous anastomoses were 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. I TABLE OF CONTENTS Page I n t r o d u c t i o n 1 H i s t o r i c a l survey 2 Acute l i g a t i o n o f p o r t a l v e i n 2 Chron ic o b l i t e r a t i o n o f p o r t a l v e i n 6 I n t e r m i t t e n t o c c l u s i o n o f p o r t a l v e i n 7 Spec ies d i f f e r e n c e 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 o f h e p a t i c v e i n s 13 L i g a t i o n o f hepa t i c a r t e r y XU Purpose o f i n v e s t i g a t i o n 1? E x p e r i m e n t a l 20 Expe r imen ta l method 20 1. Genera l 20 2. B l o o d p ressure 21 3 . B l o o d samples 22 l i . Haematocr i t e s t i m a t i o n 22 J>. Acute 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. De te rmina t ion o f communications between the p o r t a l and sys temic venous c i r c u l a t i o n 25 9. Measurement o f sp l a nc hn i c b l o o d volume 26 I I TABLE OF CONTENTS con t inued Page Observa t ions 28 1. Acute l i g a t i o n o f p o r t a l v e i n , , 28 (a) Length o f s u r v i v a l 28 (b) Observa t ions on b l o o d pressure 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 sp l anchn ic b l o o d volume 36 k. Haematocr 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 po r to - sys t emic venous anastomoses hi 6 . E x h i b i t i o n o f a n t i b i o t i c s hh G e n e r a l d i s c u s s i o n • U6 Summary 52 Tables - I t o IX 5.4-62 F i g u r e s - I t o V(b) 63-69 ACUTE LIGATION OF THE PORTAL VEIN INTRODUCTION L i g a t i o n o f the p o r t a l v e i n , which a t one time was o n l y performed by the 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 impor tance . 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 cancer o p e r a t i o n s , few s t r u c t u r e s s t i l l command r e s p e c t . Of these , the p o r t a l v e i n i s one. When d isease has spread to i n v o l v e i t s w a l l , removal o f the d i s ea sed segment i s not contemplated, 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 thought t o be f a t a l . Th i s b e l i e f i s based f o r the most p a r t on exper imen ta l work w i t h the dog. The r ev i ew o f the l i t e r a t u r e which 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 o f c h r o n i c 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 the branches o f the p o r t a l v e i n , f o r though the r e s u l t o f these incomple te l i g a t i o n s d i f f e r s markedly from t h a t o f sudden acute l i g a t i o n , the e x p l a n a t i o n s must be r e l a t e d . The l i v e r i s remarkable i n drawing i t s b l o o d supp ly from two sources , wh ich j o i n w i t h i n the parenchyma, and d r a i n b y common venous ou 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 source , the h e p a t i c a r t e r y , 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 pressure j the o the r , 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 the 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 the 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 l i v e r . When the l i t e r a t u r e i s rev iewed concern ing the r e s u l t s o f i n t e r - ference w i t h the supp ly o f b l o o d by the h e p a t i c a r t e r y there seems to be l i t t l e correspondence w i t h the 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 , n e v e r t h e l e s s , necessary t o c o n s i d e r 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 the b l o o d from these two sources b r i n g s them i n t o r e l a t i o n . HISTORICAL SURVEY 1. Acute 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 an i n v e s t i g a t i o n i n t o the fo rma t ion o f b i l e f i r s t r eco rded the 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 the dea th o f th ree dogs w i t h i n an hour . Claude Berna rd (1859) and S c h i f f (1863) independent ly found the same r e s u l t . Berna rd p o s t u l a t e d the cause o f death as a b loody c o n g e s t i o n o f the i n t e s t i n e s . " I f one suddenly t i e s a l i g a t u r e , death i s the i n e v i t a b l e consequence. The an imal d i e s h a l f t o t h r ee -qua r t e r s o f an hour l a t e r . The mechanism o f death i s easy t o unders t and . A l l the b l o o d tends t o accumulate i n the v e s s e l s o f the i n t e s - t i n e , where the a r t e r i e s c a r r y i t w i t h o u t cease , wi thou t i t b e i n g taken away immed ia t e ly . The b r a i n and o ther organs become exsanguinated and the an ima l d i e s , i n f a c t , o f anaemia." S c h i f f (1863) by 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 cons ide red t h a t the accumula t ion o f b i l e i n t o x i c a t e d the 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 hea r t i n t o the d o r s a l lymph sac o f a l i v e r l e s s f r o g . The f r o g ' s c i r c u l a t i o n f a i l e d , h i s r e f l e x e s were l o s t , and death ensued. B l o o d from a normal an ima l d i d not produce t h i s r e s u l t . These two t h e o r i e s , t h a t o f e x s a n g u i n a t i o n , and t h a t wh ich supposes t o x i c substances t o accumulate i n the b l o o d , have con t inued to have t h e i r adherents t o the presen t t i m e . S c h i f f ' s t heory appeared t o r e c e i v e support from the work o f Tappeiner (1873). I n the r a b b i t he es t ima ted t h a t 16.2$ o f the b l o o d was t r apped i n the i n t e s t i n e s a f t e r t h e p o r t a l v e i n had been l i g a t e d , bu t p robab ly l i t t l e weight can be a t t a ched to h i s f i g u r e s , f o r he es t imated the t o t a l b l o o d volume to be o n l y h-S6% o f i t s body we igh t , and t h a t 3.08$ o f i t s weight as b l o o d c o u l d be b l e d w i t h o u t death o c c u r r i n g . Neve r the l e s s , t h i s paper was much quoted, and i n 1877 Lauteribach i n P h i l a d e l p h i a thought he had d i sposed o f anaemia as the cause o f death because ( l ) the a r t e r i a l b l o o d pressure r i s e s immedia te ly f o l l o w i n g l i g a t i o n , (2) the animals never show c o n v u l s i o n s p r i o r t o dea th , (3) l i g a t u r e of the hepa t i c v e i n s , wh ich p r o - duces an analogous s t a s i s ; i s not f o l l o w e d by the same symptoms. As an a l t e r n a t i v e ^ he main ta ined t h a t an unknown p o i s o n caused death^and to prove 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 the p o r t a l v e i n o f dogs i n t o f r o g s . A l l d i e d i n th ree hours , i n a f a s h i o n s i m i l a r t o the dogs which had t h e i r p o r t a l v e i n s l i g a t e d . Th i s work was q u i c k l y r e f u t e d by Mouselraan and L ienaux i n 1885, who i n a c a r e f u l s e r i e s o f exper iments , 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 ( l ) i n j e c t e d p o r t a l v e i n b l o o d i n t o f rogs w i t h o u t r e s u l t s , (2) c o u l d main- t a i n the dog a l i v e l o n g e r , and r e s t o r e i t s p ressure 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 ro long l i f e b y l i g a t i n g the feed ing a r t e r i e s , (U) c o u l d a l l o w s u r v i v a l by r e l e a s i n g the l i g a t u r e , (5) showed t h a t complete l i g a t i o n o f the hepa t i c v e i n s o n l y was ex t remely hard to pe r fo rm. A c c o r d i n g l y they main ta ined t h a t death was indeed due t o d i m i n u t i o n o f the 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 the q u a l i t i e s o f the b l o o d , t h a t i s , i t s oxygen or carbon 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 support from Cas ta igne and B e n d e r i n 1899, who a l s o showed t h a t - h - L i f e was p ro longed by t r a n s f u s i o n and by l i g a t i o n i n t h i s ca se , o f the a o r t a above the c o e l i a c a x i s . "We have been s t r u c k , i n a l l our e x p e r i - ences , by the f a c t t h a t the aniraals d i e a b s o l u t e l y as i f they had been b l e d . " Cas ta igne and Bender a l s o quote Ne t t e r i n 1881*. as o r i g i n a t i n g the sugges t ion t h a t t o x i n s are produced i n the bowel and these , unable to be d e t o x i f i e d b y the L i v e r , cause dea th . They f e l t t h a t they had d i sp roved t h i s hypo thes i s o f N e t t e r . 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 the acute engorgement o f the i n t e s t i n e s and the manner o f death were a n a l a - gous t o death from shock. He was the f i r s t t o contemplate l i g a t i o n o f the p o r t a l v e i n as a s u r g i c a l p rocedure . U n t i l 1932 no other e f f o r t than Tappe ine r ' s seems t o have been made to measure the amount o f b l o o d t rapped 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 . This i s o b v i o u s l y the c r u x o f the ma t t e r . I f death i s due o n l y t o exsangu ina t ion i n t o the bowe l , i t shou ld be p o s s i b l e t o produce death i n a comparable t ime and manner by b l e e d i n g from a normal dog a volume o f b l o o d e q u a l i n amount t o tha t t rapped i n the g a s t r o - i n t e s t i n a l t r a c t . I n 1932, Elman and Cole made an at tempt t o measure t h i s amount o f b l o o d . They weighed the 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 g a s t r o - i n t e s t i n a l t r a c t , i n c l u d i n g the sp leen and pancreas , 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 , and compared t h i s weight w i t h the weight o f e v i s c e r a t e d organs o f normal dogs o f s i m i l a r weight and sex i n whom the p o r t a l v e i n had not been t i e d . The i n c r e a s e i n weigh t o f the organs of the 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 to be due t o the passage o f b l o o d i n t o the sp l anchn ic v a s c u l a r b e d . I n f o u r dogs t h i s i nc rease was found t o be S.2% o f the body we igh t . They, t o o , r ecorded the f a c t t h a t death c o u l d be t e m p o r a r i l y prevented by l i g a t i o n e i t h e r o f the a o r t a - 5 - above the c o e l i a c a x i s or o f the sp l anchn ic a r t e r y or by 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 ressure above the c r i t i c a l l e v e l o f 50-60 mm. o f mercury . However, death was e v e n t u a l l y caused b y gangrene o f the gu t . They c o u l d not s u b s t a n t i a t e the presence o f any t o x i n i n the t h o r a c i c duct lymph when i t was i n j e c t e d i n t o guinea p i g s , f i n a l l y , i f , 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 , the i n t e s t i n a l t r a c t was removed, death was postponed. They concluded t h a t the r a p i d death produced b y l i g a t i o n i s due t o l o s s of b l o o d f r o i m the sys temic i n t o the p o r t a l system, wh ich reduces the b l o o d pressure below t h a t compat ib le w i t h l i f e . I n 1933, McMichae l and Smirk , work ing w i t h r a t s recorded as an i n c i d e n t a l observa- 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 weight o f the gut i n c r e a s e d from an average o f 5.5$ o f the body weight t o 11.5$ and 12.5$. B o t h these r a t s d i e d i n a few hours . But i n 1935, Boyce, Lampert and McFe t r idge repea ted t h i s work u s i n g seven dogs. The i r f i g u r e f o r the i n c r e a s e i n weight o f the gut was 3.05$ o f the body we igh 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 they 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 weight w i t h o u t shock or dea th . Beyond 5.8$ the animals d i e d o f shock . T h e i r theory was t h a t death 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 was due to neurogenic shock, which produced the r a p i d i n i t i a l f a l l , and the f a l l was main ta ined by the l o s s o f b l o o d . Desp i t e these d i s c r e p a n t f i n d i n g s , p robab ly the r e s u l t o f u s i n g s m a l l numbers o f an imals i n r a t h e r crude exper iments , 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 , Devic and Gangolphe repea ted Elman and C o l e ' s work. They found t h a t 5.0$ o f the body weigh t was t r apped 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 . By u s i n g Chicago-b lue dye they 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 volumes, 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 wall, and after an inter- val, gradually obliterating the vein over a period of days. Examination of his dogs showed that an anastomosis between the great mesenteric vein and the inferior 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 collateral circulation developed. It was to this type of collateral 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 ligation of one branch of the portal vein, when f o l - lowed seven days later by ligation 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 obliter- ation of the portal vein. A l l attempts (Kunkel and Eisenmenger (19^9) - rats; Volwiler et a l . (1950); Morris and Miller ( l 9 5 l ) , Laufman et a l (19^2) - dogs) f a i l e d to produce permanent ascites because of the develop- ment of adequate collateral circulation. In any event, i t has been known since Eck (1877) f i r s t produced a to t a l bypass of the portal venous blood from the l i v e r into the inferior vena cava, that such blood was not necessary for survival. 3. Intermittent Occlusion of the Portal Vein Several authors have noted that intermittent complete occlusion of the portal vein i s tolerated (Mosselman and Lienaux - 1885, Mallet-Guy - et a l , 1950). Boyce et a l (1935) quote two Russian papers (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 for the occlusion of the total afferent supply to the l i v e r . U. Species Difference The experiments quoted above were performed mainly with the dog, although some workers used the rabbit and the rat. In these animals, death inevitably follows sudden occlusion of the portal vein. Claude Bernard ligated the portal vein of a pigeon. The bird survived the ligation, but died next morning from an unknown cause. Birds have a vein, a tributary of the renal vein, which receives blood from the t a i l and lower rectum, and then joins i t s fellow of the opposite side to form a trunk which drains the blood of the large intestine. At the upper part of the rectum i t be- comes continuous with the trunk of the veins draining the small intestine to form the portal vein. By this large communication i n the pelvis - 8 - between portal and systemic veins, blood from the viscera can flow indif - ferently into the vena cava, or into the portal 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 inferior vena cava would not flow into the portal system, but when injected into the portal vein, would flow into the vena cava. He remarked that only i n mammals does the portal vein form a closed system communicating with the systemic circulation only through the l i v e r . In 19h9 Milnes and Child showed that sudden, complete occlusion of the portal vein i n Macacus Rhesus monkeys was not f a t a l . Of 7 monkeys so ligated, a l l survived 16 to $1 days postoperatively. Portal venography showed that pelvic porto-systemic anastomoses occurred naturally, and immediately carried much of the blood. Observers had early noted that unless the ligature was placed on the hepatic side of the last portal vein tributary, survival could occur (Castaigne and Bender - 1 8 9 1 , Kusnetzow - 1 9 0 0 ) . Douglass et a l . (1951) noted survival of a dog after ligation of the portal vein, the ligature being on the intestinal side of a small pancreatic vein. Both Ore and Claude Bernard had noted that peritoneal adhesions carried portal systemic anastomoses, and that the portal vein could be ligated i n such animals. Brunschwig et a l . (19U5) had no success when attempting this, however, as an experimental method to enable dogs to survive acute ligation. It would appear that when there i s adequate collateral circulation, either by naturally occurring porto-systemic venous communication, by adhesions, or by malposition of the ligature, survival occurs after portal vein ligation. In those animals which die after ligation of the portal vein (dog, rabbit and rat), there i s no literature concerning the extent of such collateral circulation. 5. O c c l u s i o n o f the P o r t a l V e i n i n Man Neuhof proposed, i n 1913, the n e c e s s i t y f o r knowing the r e s u l t s o f l i g a t i o n o f the p o r t a l v e i n i n man. H i s s p e c i f i c i n d i c a t i o n a t t h a t t ime was suppura t ive p y l e p h l e b i t i s . On the b a s i s o f h i s own expe r imen ta l work, c a r r i e d out i n the l a b o r a t o r y o f P ro fe s so r P i c k i n B e r l i n , and the work o f o thers a l r e a d y rev iewed , he r e a l i z e d the n e c e s s i t y of an adequate c o l l a t e r a l c i r c u l a t i o n between the p o r t a l and sys temic v e i n s before l i g a - t i o n c o u l d be c o n s i d e r e d . He suggested the requirements f o r such an o p e r a t i o n , bu t he d i d not seem t o have performed i t on any p a t i e n t . Neuhof r eco rds the r e p o r t o f 6 cases by G i n t r a c (1857) where a t pos t mortem the p o r t a l v e i n was found occ luded , and the anastomotic c o l l a t e r a l s resembled those o c c u r r i n g i n c i r r h o s i s o f the l i v e r , as l a t e r d e s c r i b e d by F r e r i c h s ( l86l), Charpy (1898) and P i c k (1909). He quotes Brewer as having l i g a t e d the 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 , bu 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 which had so reduced the c a l i b r e o f the p o r t a l v e i n wh ich was s t r e t c h e d over i t as t o a l l o w the fo rma t ion o f adequate c o l l a t e r a l s . The l i g a t i o n had no e f f e c t on the p a t i e n t . In 1926 C o l p r e p o r t e d the r e s u l t s o f l i g a t i o n i n t h ree p a t i e n t s 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 . The f i r s t case, r epo r t ed i n 1915 b y Beer, had an omentopexy th ree days 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 . The l i g a t i o n had no e f f e c t on the pu l se r a t e and a t autopsy four days l a t e r t he re was evidence 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 case , 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 occu r r ed seven days l a t e r , and the autopsy showed thrombus w i t h i n the p o r t a l v e i n , w i t h no evidence o f c o l l a t e r a l c i r c u l a t i o n bu t w i t h o u t s t a s i s o f the v e s s e l s l e a d i n g to the p o r t a l v e i n . I n the l a s t case , death - 10 - occur red 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 wh ich con ta ined f l u i d b l o o d , b u t there was no autopsy r e p o r t . I n 19kh Brunschwig , i n the course o f e x t e n s i v e r e s e c t i o n s f o r carcinoma of the pancreas , d i v i d e d the p o r t a l v e i n a c c i d e n t a l l y . The p a t i e n t d i e d a f t e r two hours . I n 1°U5 a f u r t h e r case o f Brunschwig e t a l . arose i n which the p o r t a l v e i n was t i e d w i t h o u t death o c c u r r i n g , b u t a p r ev ious p e l v i c o p e r a t i o n had produced po r to - sys t emic anastomoses. In 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 . dec ided to l i g a t e the p o r t a l v e i n d e l i b e r a t e l y i n p a t i e n t s , as a two-stage procedure d u r i n g opera t ions o f r a d i c a l pancreaticoduodenectomy where the p o r t a l v e i n had been invaded by neoplasm. They had a l r e a d y t r i e d t o perform a r a d i c a l p a n c r e a t i c o - duodenectomy together 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 the p o r t a l v e i n , bu t had f a i l e d due to the massive haemorrhage which occu r red from the bed o f the pancreas . F o r t h i s r eason they planned to a l l o w t ime f o r a c o l l a t e r a l c i r c u l a t i o n t o e n l a r g e . The opera t ions were performed on two p a t i e n t s , 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 . In the f i r s t case , p r e v i o u s p o r t a l venography showed t h a t the re d i d not seem to be any o b s t r u c t i o n t o t he 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 , bu t i n the second there was a n g u l a t i o n o f the v e i n by 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 not commented upon. A p o s t - 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 anastomoses. I n an e a r l i e r - r e p o r t (1952) C h i l d e t a l . r e c o r d t h a t they 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 stage i n f i v e p a t i e n t s who had c a r - cinoma o f the stomach or head o f the pancreas . None d i e d . One had veno- g raph ic evidences o f o b s t r u c t i o n , f o u r had n o t . They f u r t h e r quote B a r c l a y ( l ? 5 l ) and Person (1951) as hav ing r e s e c t e d the p o r t a l v e i n , bu t - 11 - i n b o t h these cases the impres s ion was t h a t there was p a r t i a l o c c l u s i o n from the neoplasm. These c l i n i c a l exper iences would seem t o show tha t acute l i g a t i o n o f the p o r t a l v e i n i s not l e t h a l i n man, though i n a l l the cases r e p o r t e d there i s no c l e a r evidence o f l a c k o f p r ev ious o b s t r u c t i o n 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 , i f p re sen t , might have caused the development o f p o r t o - s y s t e m i c anastomoses. 6. L i g a t i o n o f 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) by i n j e c t i o n o f the main r i g h t and l e f t branches o f the p o r t a l v e i n , hepa t i c a r t e r y and hepa t i c duc t , showed t h a t the main p lane o f d i v i s i o n between r i g h t and l e f t lobe o f the l i v e r l i e s between the fo s sa o f the g a l l b l a d d e r and the i n f e r i o r vena cava a t the entrance o f the h e p a t i c v e i n s , thus con f i rming p rev ious 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 he re was no communication between the r i g h t and l e f t branches ac ross t h i s p lane i n the l i v e r . These obse rva t ions have been borne out by exper imen ta l work and by autopsy m a t e r i a l . I n j e c t i o n s i n t o e i t h e r o f the p o r t a l venous branches are d i s t r i b u t e d o n l y t o the i p s i l a t e r a l lobe ( B a r t l e t t e t a l . - 19lU, Copher and Dick - 1928). I f a main branch o f the p o r t a l v e i n i s l i g a t e d , the i p s i l a t e r a l lobe w i l l a t rophy (Rous - 1920, L o e f f l e r - 1936, G r i n d l a y and Bol lman - 1952). Autopsy m a t e r i a l has shown tha t o b s t r u c t i o n o f a main b ranch o f the p o r t a l v e i n has r e s u l t e d i n a t rophy o f the lobe o f t ha 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). This d i v i s i o n i n t o two lobes 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, sp l een , duodenum, upper jejunum and rectum passes to the l e f t and c e n t r a l p o r t i o n o f the l i v e r and when i n j e c t e d i n t o the lower jejunum, i l e u m and p r o x i m a l t h r ee -qua r t e r s o f the - 12 - l a r g e i n t e s t i n e , i t passes t o the r i g h t lobe ( B a r t l e t t e t a l . - 1 9 l l | ) . Copher and D i c k (1928) were ab le 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 d i r e c t l y by i n j e c t i n g t r ypan b l u e i n t o the organs , and t r a n s i l l u m i n a t i n g the p o r t a l v e i n . T h e i r work was conf i rmed b y Hahn e t a l . (19U5), who used 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 unable to 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 mesenter ic v e i n , f o r the T h o r o t r a s t they used per fused 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 eco rded by Dreyer and Bud tz -O l sen (1952) when they c a r r i e d out percutaneous s p l e n i c venography w i t h 70% d iodone . I t has a l s o been w e l l known t h a t animals w i t h an Eck f i s t u l a f a i l t o regenerate a b l a t e d l i v e r ( G r i n d l a y and Bol lman - 1952, Mann and Magath - 1922). Therefore , though o c c l u s i o n o f a b ranch o f the p o r t a l v e i n i s not f a t a l , the p o r t a l venous b l o o d i s necessary f o r the proper 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 hepa t i c a r t e r y by i t s e l f b e i n g i n s u f f i c i e n t . D e p r i v a t i o n o f the t o t a l p o r t a l venous b l o o d supp ly i s not f o l l o w e d by a t rophy , bu t r e g e n e r a t i o n i s i m p o s s i b l e . B u r n e t t e t a l . (1951) has shown i n r a t s t ha t 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 o f the l i v e r t o deve lop , whereas i n c r e a s i n g the amount o f p o r t a l venous b l o o d r e s u l t s i n an i n c r e a s e d r a t e o f l i v e r development. However, i t i s not p o r t a l venous b l o o d which i s e s s e n t i a l f o r r e g e n e r a t i o n . C h i l d e t a l . (1953) c a r r i e d ou t , 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 , so t ha 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 the i n f e r i o r vena cava ; the i n t r a - hepa t i c p o r t a l bed was f i l l e d w i t h sys temic venous b l o o d . Approx imate ly one month l a t e r , p a r t i a l hepat:ec tomy was c a r r i e d o u t . I n normal dogs, the l i v e r regenera ted to 7S% o f the weight o f the e x c i s e d p o r t i o n ; i n those 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 , the r egene ra t ion was $0%. The - 13 - s u b s t i t u t i o n o f sys temic venous b l o o d f o r p o r t a l venous b l o o d s t i l l a l l o w s adequate r e g e n e r a t i o n . There does not appear t o be any f a c t o r p e c u l i a r to p o r t a l venous b l o o d which i s necessa ry f o r l i v e r r e g e n e r a t i o n . The d i f - ference i n amount regenera ted i s p robab ly t o be a t t r i b u t e d t o the l e s s e r f l o w o f b l o o d i n the i n f e r i o r vena cava below the hepa t i c v e i n s , when compared w i t h the p o r t a l venous f l o w . 7 . L i g a t i o n o f the Hepat ic V e i n s . Whereas l i g a t i o n of the p o r t a l v e i n i s r e l a t i v e l y easy , a l l i t s t r i b u t a r i e s e v e n t u a l l y forming a s i n g l e v e s s e l w e l l p l a c e d f o r a l i g a t u r e , l i g a t i o n o f the h e p a t i c v e i n s i s most d i f f i c u l t . Simonds and Brandes (192$) 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 hepa 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 . They used dogs, and passed a rubber tube , 0 .5 cm. i n d iameter , 2 f e e t long around the l i v e r i n such a way t ha t t r a c t i o n on the ends o f the lbube, w i t h counter t r a c t i o n on the l i v e r , would produce o c c l u s i o n o f the hepa t i c v e i n s o n l y . Such o c c l u s i o n p r o - duced a p r e c i p i t a t e 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 ressure w i t h i n the p o r t a l v e i n . Engorgement of the l i v e r was marked, t h a t o f the i n t e s t i n e s not so marked. The l i v e r engorgement produced a c e s s a t i o n o f f l o w i n the hepa t i c a r t e r y . Once the p ressure 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 ma in ta ined , no f u r t h e r f a l l o c c u r r e d . I t has been shown, however, t ha t i t i s r e a l l y v e r y hard even i n t h i s way t o ensure complete o c c l u s i o n o f the hepa t i c v e i n s . Simonds was i n t e r e s t e d i n the problem as an e x p l a n a t i o n of the e f f e c t o f peptone "shock" i n dogs. He and Arey (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 the w a l l s o f the hepa t i c v e i n s o f the dog and suggested t h a t such muscle , thrown i n t o spasm upon the i n t r o d u c t i o n o f the p r o t e i n - U* - t o wh ich the an ima 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 through the l i v e r . I t i s d i f f i c u l t 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 the p o r t a l v e i n , f o r i t i s no t p o s s i b l e t o determine whether the hepa t i c v e i n s were comple t e ly l i g a t e d , i n the experiments c i t e d . Armstrong and R icha rds (I9kk) succeeded i n a c h r o n i c l i g a t i o n o f the hepa t i c v e i n s i n three dogs w i t h s i m i l a r r e s u l t s . B o l t o n ( 19LU), u s i n g c a t s and monkeys, noted t h a t complete l i g a t i o n , or more than t h r e e - f i f t h s o c c l u s i o n o f the i n f e r i o r vena cava above the hepa t i c v e i n s r e s u l t e d i n death w i t h i n a few hour s . When the o c c l u s i o n was between two- f i f t h s and t h r e e - f i f t h s of the c a l i b f e o f the v e i n a s c i t e s appeared which o n l y l a s t e d f o r two to th ree months, u n t i l adequate c o l l a t e r a l s deve loped . Subsequent i n v e s t i g a t o r s have a l s o been content t o l i g a t e the i n f e r i o r vena cava a t the diaphragm ( K i r s c h n e r e t a l . - 19̂ 5, Laufman e t a l . - 1951, Berman and H u l l - 1952, M i l n e s - 1952, J e f f e r s o n e t 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 isappeared w i t h i n a few months. K i r s c h n e r e t a l . (19U5) no ted , as a major c o l l a t e r a l t runk , the presence o f a l a r g e diaphragmat ic v e i n which j o i n s a l e f t hepa 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 . Hepa t ic 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 the hepa t i c a r t e r y has been a con ten- t i o u s sub jec t f o r many y e a r s . When the dog was used as the expe r imen ta l a n i m a l , i t was r e a l i z e d as l ong ago as 1898 (Doyon and Dufour t ) t h a t s u r v i v a l was the 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 the other branches o f the c o e l i a c a x i s , and t h i s was conf i rmed as the - 1$ - years went by (Haberer - 1905, S e g a l l - 1923). I t i s no t s u f f i c i e n t t o l i g a t e the hepa t i c a r t e r y j u s t before 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 ph ren ic v e s s e l s c o n t r i b u t e branches between the capsule and ne ighbor ing v e s s e l s , and f u r t h e r v e s s e l s run a long the l i g a - mentum venosum, and a long p o r t a l v e i n , vena cava , and common b i l e duct ( J e f f e r s o n e t a l . - 1952). F u r t h e r , branches may a r i s e e a r l y , and pass t o the l o b e , thus bypass ing the 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 the r a b b i t and guinea p i g which l eads t o t h e i r dea th when a c e n t r a l b ranch i s l i g a t e d . The ca t behaves i n the same manner as the dog (Behrend e t a l . - 1922). In man, the r e s u l t s o f l i g a t i o n are based on c l i d c a l obse rva t ions i n cases having 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 o f the a r t e r y . In a r ev i ew o f 28 cases t o 1932, Graham and C a n n e l l conf i rmed 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 hepa t i c a r t e r y t r u n k , o r the a r t e r y p rope r , before the r i g h t 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 en su ing . Where the l i g a t i o n takes 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 the 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 tudy has been made i n such cases , f o r i t s impor tance , as w i l l be seen, has o n l y l a t e l y been r e c o g n i z e d . I n the 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 the hepa 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 of the hepa t i c a r t e r y from i t s o r i g i n a t the c o e l i a c a x i s to i t s disappearance i n t o the l i v e r , and by check ing the e f f i c a c y o f the 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 i n t o the a o r t a , i t was thought t h a t the source o f a l l hepa t i c a r t e r i a l b l o o d was removed. But others have p o i n t e d out t h a t i n dogs the o n l y c e r t a i n - 16 - evidence o f the absence o f a r t e r i a l b l o o d , i s the c a r e f u l postmortem d i s - s e c t i o n o f a l l v e s s e l s , the a o r t a having 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 . ( J e f f e r s o n e t a l . - 1902, Popper e t a l . - 1952). P rev ious 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 to 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 an a c c i d e n t a l o b s e r v a t i o n o f Markowi tz , Rappaport and S c o t t (19U9) which f u r n i s h e d a c l u e t o the cause o f dea th . During attempts t o a r t e r i a l i z e the p o r t a l v e i n , by u s i n g a s p l e n i c a r t e r y t o s p l e n i c v e i n anas tomosis , p e n i c i l l i n was e x h i b i t e d t o cover any breaks i n the a s e p t i c t e c h n i q u e . A t the c o n c l u s i o n o f the o p e r a t i o n the hepa t i c a r t e r y was l i g a t e d as comple t e ly as p o s s i b l e . The dog s u r v i v e d , bu t a t postmortem examinat ion l a t e r the anastomosis was found t o be thrombosed. Thus p e n i c i l l i n seemed t o have had the power o f i n h i b i t i n g the f a t a l e f f e c t o f hepa 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 conf i rmed many t imes (Davis 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 the a n t i - b i o t i c i n h i b i t s the growth o f anaerobes and the 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 the development o f an adequate c o l l a t e r a l a r t e r i a l supp ly (Markowitz and Rappaport - 195l, T a n t u r i e t a l . - 19^0). I f such an a r t e r i a l c o l l a t e r a l supp ly does not deve lop , the an ima 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). Bu t such an e x p l a n a t i o n does not account f o r a l l the f a c t o r s i n v o l v e d . This i n v e s t i g a t i o n , i n f a c t , had i t s f i r s t beg inn ings i n some i n v e s t i g a t i o n s t h a t Jackson had been making i n t o the 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 the 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 (Jackson - 1909)• He asked Wolbach and S a i k i i n the same year 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 which he had found i n the l i v e r . - 17 - They used 23 dogs, k i l l e d them, bu rn t the abdominal w a l l , and removed the g rea t e r p o r t i o n o f the l i v e r . The p i e c e s were i ncuba ted 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 anaerobic c o n d i t i o n s , the re were marked changes a f t e r 18 t o 2h h o u r s . The l i v e r was s o f t , green and r a n c i d , w i t h much gas p r o d u c t i o n . C o n t r o l c u l t u r e s o f the sp leen and k i d n e y f a i l e d , (except i n one case) t o produce the same organisms. The b a c i l l u s was 8-9/u. 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 f i l t r a t e from the l i v e r 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 guinea p i g s o r o ther dogs . Two l i v e r s were s t e r i l e . This organism was cons ide red 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 o f dog ' s l i v e r . There the mat ter r e s t e d f o r 16 yea 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. per k i l o o f body we igh t ) detached and l e f t f r ee i n the p e r i t o n e a l c a v i t y , produced death 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 Drags ted t (1930) by a u t o e l a v i n g the p i e c e o f l i v e r and then 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 dea th . They a l s o showed t ha t l i v e r ob ta ined by Caesa r i an s e c t i o n from a dog foe tus was innocuous . However, the work was repeated by v a r i o u s o t h e r s , and the r e s u l t s ceased t o be as c l e a r - c u t . 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 the problem. They f i r s t p o i n t e d out t h a t the organism i n the dog ' s l i v e r was not C I . W e l c h i i o f t o x i c s t r a i n , bu t a s t r i c t anaerobe, t h e r m o p h i l i c and o f the nonsucrose fe rment ing , p u t r e f a c t i v e gas- forming type o f the genus C l o s - t r i d i u m . Th i s same organism was p resen t i n the muscle o f dogs, and i t f a i l e d t o produce an e x o t o x i n . As a r e s u l t they wondered whether i t had any s i g n i f i c a n c e i n d i s e a s e . I f over 30 grams o f l i v e r was implan ted , a l l dogs d i e d (though t h i s was n e a r l y 6 t imes g rea t e r than the amount t h a t Mann found necessary t o cause d e a t h ) . I n t h i s case there 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 the p e r i t o n e a l c a v i t y . By sepa ra t i ng the parenchymal elements from the l i v e r connec t ive t i s s u e , b i l e duc ts and b l o o d v e s s e l s , they found t h a t i m p l a n t a t i o n of the l a t t e r elements was a s s o c i a t e d w i t h the p i c t u r e o f shock and p e r i t o n i t i s . F u r t h e r , they found t h a t i f the l i v e r was incuba ted and then s t e r i l i z e d b y hea t , death occur red p rompt ly , bu t was not due t o b a c t e r i a . They a l s o showed t h a t b i l e s a l t s cause i n t ense i r r i t a t i o n o f the p e r i t o n e a l sur faces w i t h the p r o d u c t i o n o f severe shock . l i g a t i o n o f the hepa t i c a r t e r y w i l l p r o - duce n e c r o s i s o f the g a l l b l adde r and a l l o w the escape of b i l e i n t o the p e r i t o n e a l c a v i t y . Mason and Davidson (l°2i|-25) conf i rmed 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 , bu t d i d not 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 Hrd ina (1931) because they found t h a t a u t o c l a v e d l i v e r produced 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 - cons ide red t h a t the r e a c t i o n was provoked by the s t e r i l e m a t e r i a l . Dvorak (1932) found t h a t ground l i v e r always k i l l e d , bu t s t e r i l e l i v e r never d i d so; a kO ml suspens ion of anaerobes was necessary 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 f l u i d 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 h o s t . B i l e s a l t s were not p resen t i n the normal l i v e r of a dog i n su 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 concluded t h a t no t o x i n produced i n the l i v e r was r e s p o n s i b l e f o r dea th , b u t t ha t anaerobic b a c t e r i a or t h e i r t o x i n s were the cause . Boyce and McFet r idge (1937) repeated many o f these exper iments , w i t h o u t however g i v i n g c l e a r accounts o f t h e i r expe r imen ta l methods. As they seemed to be ab l e to produce - 19 - death w i t h s t e r i l e au toc l aved 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 no t cause death by the i n t r a p e r i t o n e a l or in t ravenous i n j e c t i o n o f the 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 , they dec ided t h a t the r o l e o f the 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 hepa t i c a r t e r y had been comple t e ly 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 l i g a t i o n . The c u l t u r e s remained p o s i t i v e u n t i l dea th . 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 Clostridia d i sappeared from the s t o o l s . P r e - o p e r a t i v e p e n i c i l l i n had no e f f e c t , 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 e f f e c t i v e , and the b l o o d c u l t u r e remained n e g a t i v e . S i m i l a r r e s u l t s were found when aureomycin was used i n s t e a d o f p e n i c i l l i n . Eze (1952) a l s o found t h a t a s i n g l e dose o f potass ium p e n i c i l l i n G subcutaneously immedia te ly a f t e r o p e r a t i o n p r o t e c t e d the dogs. Nelson (195l) showed t h a t in t ravenous 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 can produce r a p i d death i n dogs i n 2 t o 3 hours w i t h a p i c t u r e o f me tabo l i c a c i d o s i s . Thus, the re are 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 the cause o f death i s due t o anaerobic organisms and t h e i r t o x i n s and those 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 which are l e t h a l . Human l i v e r i s g e n e r a l l y cons ide red t o be s t e r i l e (LewisandWangensteen - 1950, Romieu and Brunschwig - 1951, Sborov e t a l . - 1952). PURPOSE OF INVESTIGATION Th i s r ev iew 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 there i s no disagreement tha t the r e s u l t o f sudden acute 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 dea th , there i s disagreement about the cause o f - 20 - d e a t h . I t i s not c e r t a i n l y known what e f f e c t s acute l i g a t i o n has i n man, or even i n o ther a n i m a l s . Th i s l a c k o f agreement extends a l s o to the e f f e c t s o f acute l i g a t i o n o f the hepa t i c a r t e r y and the hepa t i c v e i n s . The e f f e c t s o f acute l i g a t i o n o f the p o r t a l v e i n i n man are s t i l l based on the r e s u l t s of an ima l expe r imen ta t ion , b u t t h i s i s s h i f t i n g sand, i f even these r e s u l t s a re u n c e r t a i n . Before a b l a t i v e ope ra t ions are under- t aken , more c e r t a i n i n f o r m a t i o n must be ob ta ined , and i t i s the purpose o f these i n v e s t i g a t i o n s t o employ recen t t e c h n i c a l advances i n a r e s e a r c h o f the problem as i t a f f e c t s the dog . PLAN OF EXPERIMENTS F o l l o w i n g acute l i g a t i o n o f the 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 p o r t o - s y s - temic anastomoses. The p o s i t i o n o f these 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 the v a l i d i t y o f the method employed was examined. The normal c a p a c i t y o f the sp l anchn ic v a s c u l a r bed was measured. Fu r the r i n v e s t i g a t i o n s which are r e q u i r e d have been i n d i c a t e d . The methods employed are d e t a i l e d under the heading "Exper imen ta l " and the r e s u l t s ob ta ined are r eco rded under "Obse rva t ions" . 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 se t o f o b s e r v a t i o n s , the 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. Genera l Pound dogs were used , unse l ec t ed as t o we igh t , sex or g e n e r a l c o n d i t i o n . 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 water r e s t r i c t i o n s . P r i o r t o b e i n g a n a e s t h e t i z e d , they were encouraged t o empty t h e i r b l a d d e r s , and were then weighed. Anaes thes i a was produced by the i n t r a - 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 , u s i n g 30 mgm/kg body we igh t . The dogs were i n t u b a t e d w i t h an endo t rachea l tube and p l aced 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 , care b e i n g t aken to reduce b l e e d i n g t o a minimum; (by measuring the i nc r ea se i n weight o f d r y gauze sponges used f o r mopping, b l o o d l o s s d i d no t exceed 10 t o 20 m l . ) . Dur ing 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 to do s o , u s u a l l y by A l l i s t i s s u e fo rceps j i f i m p o s s i b l e , the wound was p r o t e c t e d by towels soaked i n s a l i n e . The l e n g t h o f any experiment seldom exceeded 2 hou r s , and i t was u s u a l l y unnecessary t o g i v e a f u r t h e r dose o f sodium p e n t o b a r b i t a l . The an imals were unconscious d u r i n g the whole o f the exper iment . They r e c e i v e d no in t ravenous therapy nor f l u i d by oesophageal t ube . The temperature w i t h i n the o p e r a t i n g room was f a i r l y cons tan t between 7 0 ° and 7 5 ° F . The i n s t a n t o f death was t aken as the l a s t c o n t r a c t i o n o f the l e f t v e n t r i c l e o f the hea r t s u f f i c i e n t t o be recorded by a mercury b l o o d pressure 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 . B l o o d Pressure A cont inuous r e c o r d o f the b l o o d pressure was ob ta ined by a mercury manometer. The l e f t common c a r o t i d a r t e r y was exposed by 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 cannula ted w i t h a No. 12 b lun t - ended cannula wh ich was t i e d i n . The cannula 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 wh ich r e s i s t s l a t e r a l expans ion o f i t s w a l l s ( A r s t e t a l . - 1951) . - 22 - 3 . B l o o d Samples These were ob ta ined 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 s y r i n g e s (jaques e t a l . - 19U6). U. Haematocr i t E s t i m a t i o n Wintrobe*s mix ture was used as an a n t i c o a g u l a n t , and the samples o f b l o o d were spun f o r 30 minutes a t 2,210 R . C . F . The samples used were p o r t i o n s o f the b l o o d ob ta ined 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 needle was i n s e r t e d d i r e c t l y i n t o the p o r t a l v e i n . I t was found t h a t c l o t s formed of ten i n t h i s p o r t i o n o f the v e i n , and the re fo re hepa r in was u s u a l l y g i v e n i n these experiments (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 t l ie f t a r t a l V e i n Under the s tandard 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 i d e n t i f i e d , and the o v e r l y i n g per i toneum o f the f ree edge of the l e s s e r sac d i v i d e d . 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 hepa t i c s i d e of the l a s t t r i b u t a r y , and the ends brought out through the abdominal wound. The t r a c t i o n necessa ry t o 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 the b l o o d p r e s s u r e , and t ime 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 no rma l . When the p ressure f i n a l l y s e t t l e d , the l i g a t u r e was t i e d , d i s t u r b i n g the v i s c e r a as l i t t l e as p o s s i b l e . The abdominal wound was c l o s e d w i t h A l l i s f o r ceps , and the dog l e f t und i s tu rbed u n t i l dea th . When s imultaneous records were ob ta ined o f b o t h i n t r a - a r t e r i a l p res su re and p o r t a l venous p r e s su re , the a r t e r i a l p ressure was ob ta ined u s i n g a mercury manometer as de sc r i bed above. The p o r t a l venous pressure - 23 - • was ob ta ined by 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 l igament , u s i n g s i z e 16 po ly thene 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 the main s p l e n i c v e i n . The t u b i n g was then connected t o a p h y s i o l o g i c a l p ressure t r ansduce r (Statham model P23A) , the output be ing a m p l i f i e d by a Brush u n i v e r s a l a m p l i - f i e r (Model B L 3 2 0 ) . A cont inuous i n k r e c o r d was o b t a i n e d by 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 prevented 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 de te rmina t ions were made u s i n g Reeve and V e a l l ' s (19^9) m o d i f i c a t i o n f o r the procedure o f Hevesy and Zerahn (19^2) . Ten m l . o f venous b l o o d was wi thdrawn from a forepaw v e i n o f the dog i n t o a 10 m l . s y r i n g e c o n t a i n i n g h e p a r i n . E i g h t m l . o f t h i s b l o o d was incuba ted 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 ee 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 - mate ly 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 water b a t h a t a cons tan t temperature o f 3 7 ° C . The c e l l s were then separa ted from the 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 . The s e p a r a t i o n and r e suspens ion was done th ree t i m e s . Two m l . o f the f r e s h l y p repared suspens ion of 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 emora 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 mix ing t o occur , 10 m l . o f b l o o d was withdrawn from the c o n t r a l a t e r a l femora 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 beaker c o n t a i n i n g sodium c i t r a t e c r y s t a l s as an a n t i c o a g u l a n t and powdered saponin t o produce l y s i s of the r e d c e l l s . F i v e 1 m l . samples of t h i s b l o o d were counted 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 b e t a Geiger coun te r . r 2k - The a c t i v i t y o f the specimen o f b l o o d withdrawn from the femora l a r t e r y was compared w i t h the a c t i v i t y of the o r i g i n a l 2 m l . suspension o f l a b e l l e d r e d c e l l s . The a c t i v i t y o f t h i s was ob ta ined by u s i n g the same 2 m l . s y r i n g e t o draw up the suspens ion , and d i l u t i n g i t t o approx imate ly the same volume as the b l o o d volume o f the dog by i n j e c t i n g i t i n t o a Winches ter b o t t l e c o n t a i n i n g 2000 m l . o f wate r , and aga in count ing 5 samples o f 1 m l . o f the d i l u t i o n f o r a c t i v i t y . I f the t o t a l a c t i v i t y o f the l a b e l l e d r e d c e l l s i s A counts per second, and the a c t i v i t y o f 1 m l . o f the b l o o d withdrawn from the an imal i s B counts per second then the b l o o d volume, V , i s g i v e n by the formula BV = A , or V • § . When a second b l o o d volume de t e rmina t i on was r e q u i r e d , 10 m l . o f b l o o d was withdrawn from the i p s i l a t e r a l f emora l a r t e r y , and counted f o r background a c t i v i t y . 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 i n t o the femora l v e i n no t p r e v i o u s l y used , and a g a i n , a f t e r $ minutes , 10 m l . o f b l o o d was ob ta ined from the femora l a r t e r y no t p r e v i o u s l y u sed . By i n s e r t i n g the needle (22 SWG) a t an angle i n t o the a r t e r y , and by f i n g e r pressure on the hole f o r th ree minutes a f t e r w i t h d r a w a l , no b l o o d escaped desp i t e h e p a r i n i z a t i o n . 7. 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 rder t o d i s c o v e r whether adequate t ime was a l l o w e d f o r mix ing 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 , two types o f experiments were c a r r i e d o u t . (a) S e r i a l E s t i m a t i o n o f the A c t i v i t y A two-way s top-cock a t t ached t o an 18 SWG needle was i n s e r t e d i n t o the l e f t f emora 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 f emora l v e i n . A t 2 minute i n t e r v a l s t h e r e a f t e r 2 m l . samples o f b l o o d were ob ta ined from the f emora 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 to f l o w through the needle and s top-cock to f l u s h out the b l o o d remain ing from the p rev ious sample. To o b v i a t e c l o t t i n g w i t h i n the need le , h e p a r i n was g i v e n t o the dog. (b) Continuous Record o f A c t i v i t y The femora l v e s s e l s on bo th s i d e s were exposed. On one s i d e the femora l a r t e r y was d i v i d e d and cannula ted w i t h No. 16 po lye thy l ene 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 arranged so t h a t a h e l i x was formed, through which the 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 coun t e r s , w i r e d i n p a r a l l e l (Tracer L a b . TGC-2). Two m l . o f P32 l a b e l l e d r ed c e l l s were 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 f emora l v e i n . By means o f a r a t e meter (Nuclear ins t rument c o r p o r a t i o n , Model l6l5 - B ) arranged t o r e c o r d through an E s t e r l i n e Angus g raph ic ammeter r e c o r d e r , a cont inuous 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 the c i r c u l a t i n g b l o o d c o u l d be o b t a i n e d . In o rde r to check the patency o f the system, a b l e e d i n g tap was p l a c e d on the d i s t a l s i d e o f the h e l i x . Hepar in was g i v e n to prevent c l o t t i n g w i t h i n the t u b i n g . 8 . De te rmina t ion o f Communications Between the P o r t a l and Systemic 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 , dogs were anaes the t i z ed w i t h sodium p e n t o b a r b i t a l , the abdomen opened, and the p o r t a l v e i n l i g a t e d t o r a i s e the p o r t a l venous p r e s su re , thus opening up any s m a l l anastomoses w i t h the sys temic 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 the a n t e r i o r ches 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 , and a l l o w i n g b l o o d to f l o w from b o t h ends . Hepar in 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 mgm/ki lo o f body weigh t ) i n order t o prevent b lockage 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 . The l i g a t u r e around the p o r t a l v e i n was then c u t . A cannula was p l a c e d i n the t h o r a c i c a o r t a and a t t ached to a water t a p . A t a p ressure o f 150-200 mm. o f mercury the b l o o d w i t h i n the v e s s e l s was washed ou t , dra inage be ing p r o v i d e d by a cannula w i t h i n the i n f e r i o r vena cava , and another i n the p o r t a l v e i n . Washing was con t inued u n t i l the water r e t u r n e d c l e a r . Th i s u s u a l l y took about one hour . The water was then a l l o w e d to d r a i n out and two hours l a t e r , l a t e x (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 through the cannula w i t h i n the p o r t a l v e i n a t a cons tan t p res su re o f 1 0 0 mm. o f mercury. The i n j e c t i o n m a t e r i a l f lowed q u i c k l y and e a s i l y t o f i l l a l l the s m a l l venu les o f the p o r t a l venous system. I n order 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 main ta ined a t t h i s p ressure f o r one h o u r . A t the c o n c l u s i o n o f the i n j e c t i o n , the p o r t a l v e i n cannula was c l o s e d , and the an ima l kep t ove r - n i g h t t o a l l o w the l a t e x to s e t . I t was then c a r e f u l l y d i s s e c t e d , the symphysis pub 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 communicat ions. The diaphragm was not i n c i s e d p r i o r t o 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 f i l l i n g o f the communications a t the lower end o f the oesophagus. 9. Measurement of Sp lanchn ic 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 es t imated u s i n g l a b e l l e d r e d c e l l s , the i n j e c t e d c e l l s are e q u a l l y d i s t r i b u t e d throughout 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 feed ing 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 are s imu l t aneous ly occ luded , 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 normal quota 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 . A measure o f the t o t a l a c t i v i t y o f t h a t organ w i l l t he re fo re g ive the q u a n t i t y o f b l o o d con ta ined w i t h i n the organ . Pound dogs anaes the t i z ed w i t h sodium p e n t o b a r b i t a l i n t r a v e n o u s l y were u s e d . Ten m l . o f b l o o d was ob t a ined from the r i g h t f emora l v e i n f o r i n c u b a t i o n w i t h P ^ * A f t e r approx imate ly one and a h a l f hours , the abdo- men was opened, and l i g a t u r e s were p l a c e d around the i n t r a - a b d o m i n a l oesophagus and around the rectum as c l o s e to 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 rea t mesenter ic a r t e r y were i d e n t i f i e d , and w i t h the minimum of d i s s e c t i o n were c l e a r e d so tha t a heavy haemostat c o u l d occ lude 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 mesenter ic 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 es t imated i n the u s u a l manner w i t h the 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 the sample o f b l o o d f o r de t e rmina t ion o f the b l o o d volume, clamps were a p p l i e d s imu l t aneous ly to the p o r t a l v e i n and grea t mesenter ic a r t e r y . By d i v i d i n g these v e s s e l s , c u t t i n g across the oesophagus and rectum, and c u t t i n g the attachment o f the mesentery t o the p o s t e r i o r abdominal 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 lower oesophagus t o the lowes t p a r t o f the rectum, toge ther w i t h s p l e e n and pancreas , w i t h o u t l o s i n g any o f the con t a ined b l o o d . T h e s e organs were then p l a c e d i n a l a r g e j a r and concen t ra ted 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 approx imate ly U8 hours dur ing which time the decay o f r a d i o a c t i v e - 28 - phosphorus occu r red a t a known r a t e . The f a t rose t o t he sur face and was d i s c a r d e d , f o r i t con t a in s o n l y about 1% o f the a c t i v i t y compared w i t h an e q u a l q u a n t i t y o f l i q u o r . The d i m i n u t i o n o f count ing r a t e which occurs 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 used , compared w i t h the coun t ing r a t e i n wa te r , i s o n l y 3 . 3 $ . The s p e c i f i c g r a v i t y o f the l i q u o r i n three experiments 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 the l i q u o r was measured and counts were then made of the a c t i v i t y o f 10 m l . samples . Having c o r r e c t e d f o r the n a t u r a l decay o f the a c t i v i t y o f the r a d i o a c t i v e phosphorus, the t o t a l a c t i v i t y con t a ined w i t h i n 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 was o b t a i n e d . I f the t o t a l a c t i v i t y o f the 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 per second and the a c t i v i t y o f 1 m l . o f the b l o o d withdrawn from the an ima l a f t e r mix ing has occu r red i s B counts per second, then the 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 by the formula BV » A . A l s o i f the a c t i v i t y o f the l i q u o r o f the d i g e s t e d organs i s X counts per second per m l . , and the t o t a l volume i s Y , then the t o t a l a c t i v i t y o f the l i q u o r i s XY counts per second. By s imple p r o p o r t i o n , i f the volume o f the b l o o d con ta ined w i t h i n the d i g e s t e d organs i s V I then V i „ XY ^ XY x V — — or Vn = V A 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) Leng th 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 ime f o l l o w i n g acute l i g a t i o n under th ree d i f f e r e n t c i r cums tances , ( i ) acute l i g a t i o n o f the p o r t a l v e i n o n l y , ( i i ) acute l i g a t i o n o f the p o r t a l v e i n , toge ther w i t h l i g a t i o n o f the oesophageal anastomotic v e i n s , ( i i i ) acute l i g a t i o n o f the - 29 - p o r t a l v e i n , the dogs b e i n g g i v e n h e p a r i n . D i s c u s s i o n . Acute l i g a t i o n i n lU dogs caused death i n an average o f 79.7 + ( - 18 .9) minutes , a f i g u r e wh ich i s i n a c c o r d 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 dogs, the t ime o f s u r v i v a l was shortened to 56.0 ( - 8 .5) minu tes . I n 9 dogs w i t h acute l i g a t i o n o f the p o r t a l v e i n , w i thou t oesophageal l i g a t u r e , b u t g i v e n h e p a r i n (10 mgs/kg) , t ime o f s u r v i v a l was 88.6 (- 23.26) minu tes . 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 or w i t h o u t oesophageal l i g a t u r e s , bu 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 or w i t h o u t h e p a r i n . I n fou r dogs the 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 the re fo re i ncomple t e . Two o f these dogs s u r v i v e d , and were k i l l e d a f t e r two hou r s . I n one, the t r i b u t a r y measured 1.5 mm. i n d iameter , and the sys temic b l o o d pressure a t s a c r i f i c e was 90 mm. Hg . Of the other two dogs which d i e d , one was an o l d dog, w i t h a t r i b u t a r y measuring 1.5 mm., the o ther was a young dog, w i t h a t r i b u t a r y measuring 0.5 mm. i n d iamete r . (b) Observa t ions on B l o o d Pressure Immediately 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 a r t e r i a l p ressure drops r a p i d l y i n the f i r s t few minutes and then more s l o w l y t o reach a p l a t e a u a t 30-U0 mm. Hg . a f t e r about 19-20 minu tes . I t s t ays 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 d e a t h . - 30 - I f s imultaneous r eco rds are t aken o f the p o r t a l venous pressure and a r t e r i a l p ressure i t i s shown t h a t the p o r t a l venous p ressure r i s e s from a p r e l i g a t i o n l e v e l o f around 7 mm. Hg. t o a maximum o f 50-60 mm. Hg. i n about 2 mins ; t h e r e a f t e r the p o r t a l venous p ressure d e c l i n e s p a r a l l e l i n g the f a l l i n the sys temic a r t e r i a l pressure 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 t y p i c a l r e s u l t i s shown i n F i g . I . D i s c u s s i o n . F o l l o w i n g l i g a t i o n , b l o o d i s c o n t i n u o u s l y s u p p l i e d t o the s p l a n c h n i c v e s s e l s , from which i t cannot escape . As the c i r c u l a t i n g b l o o d volume i s r a p i d l y reduced, so the sys temic b l o o d pressure w i l l f a l l , u n t i l i t i s equa l to the l e v e l t o which the p o r t a l venous pressure r i s e s . Whi le the p ressures remain e q u a l , d u r i n g the p e r i o d o f the p l a t e a u , the o n l y b l o o d e n t e r i n g the sp l anchn ic v a s c u l a r bed w i l l be t o r e p l a c e the b l o o d escap ing from the bed b y the po r to - sys t emic anastomoses, and the b l o o d l o s t by haemorrhage i n t o the bowel w a l l . The s p l anchn i c bed i s t o a l l i n t e n t s exc luded 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 anastomoses are occ luded the e x c l u s i o n i s more comple te . Therefore a measurement o f the b l o o d volume du r ing t h i s p e r i o d w i l l measure o n l y the c i r c u l a t i n g sys temic p o r t i o n . I t i s i n t e r e s t i n g t o note t h a t there i s no apparent at tempt t o compensate f o r the p o o l i n g o f the b l o o d 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 . There are two p o s s i b l e e x p l a n a t i o n s , ( i ) any at tempt by the dog to compensate f o r the 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 , which w i l l cause f u r t h e r b l o o d t o be l o s t i n t o - 31 - the sp l anchn ic b e d . The b l o o d pressure records show no evidence o f t h i s , ( i i ) compensation may f a i l to o c c u r . Peck and Grover ( l °52) have suggested 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 ressure i s r e f l e x i n na tu r e , w h i l e the ensuing s lower 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 no t p o s s i b l e f o r the r e d u c t i o n i n b l o o d volume to be so g rea t as t o produce such a f a l l i n b l o o d pressure i n the t ime recorded , bu t t h i s p o s s i b i l i t y cannot be exc luded u n t i l the r e d u c t i o n i n b l o o d volume, and the r a t e a t wh ich i t p roceeds , i s known. 2. B l o o d Volume Es t ima t ions The r e s u l t s of e l even experiments are summarized i n Table 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 anaes thes ia and the trauma a t tendant on the abdominal i n c i s i o n , the 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 . per 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 o c c l u s i o n o f the p o r t a l v e i n and 10 minutes a f t e r l i g a t i o n of the oesophagus and i t s v e s s e l s , the average sys temic 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 . or 57.9$ (± 8.77) o f the o r i g i n a l b l o o d vo lume. Table I I I l i s t s the t r u e counts per second pe r 10 m l . u t i l i z i n g the cons tan t geometry p r o v i d e d by the same V e a l l counter f o r each o f 5 counts f o r each exper iment . 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 coun t ing r a t e o f the sys temic b l o o d f e l l t o 85.0$ (- 13.8) o f the 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 rose t o 117.2% (* 15.9) o f 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 , the average coun t ing r a t e o f the p o r t a l venous b l o o d rose o n l y - 32 * 1.3$ ( - 7.5$) above the background count f o r the b l o o d immedia te ly p r i o r to the second i n j e c t i o n , whereas the average sys temic count rose 178.8$ (i 8 0 . 2 ) . In 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 under taken, except 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 the average p o r t a l venous b l o o d count ing r a t e o f 17.8$ (- 22.2) was no ted , when the average systemic b l o o d coun t ing r a t e rose 175.6$ (i 5 3 . 0 ) . This i n d i c a t e d the degree o f leakage o f l a b e l l e d r e d c e l l s i n t o the sp l anchn i c v a s c u l a r bed , when these main anastomotic channels were not 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 experiments t h a t the s i t u a t i o n o f the main anastomoses between the systemic 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 . D i s c u s s i o n . I t i s p o s s i b l e t o c a r r y out accura te de te rmina t ions o f c i r c u l a t i n g b l o o d volumes by 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). I n t h i s experiment the de te rmina t ions were made u s i n g Reeve and V e a l l ' s (I9k9) m o d i f i c a t i o n of the method o f Hevesy and Zerahn . By u s i n g the V e a l l coun te r , i t i s no t necessary t o es t imate the haematocr i t t o c a l c u l a t e b l o o d volume, f o r the a c t i v i t y o f whole b l o o d i s counted, and i t i s unnecessary 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 rapped w i t h the r e d b l o o d c e l l s . 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 obse rve r s , Table I V . - 33 - In g e n e r a l , i n human p a t i e n t s the va lue g i v e n by the P^2 method has been found t o be lower than t ha t based on the dye T-1821+. The va lue f o r dogs ob ta ined i n these experiments (76 .9 ml /kg) i s remarkably c o n s i s - t e n t , bu t neve r the l e s s i t cannot be compared w i t h those g i v e n by other worker s , f o r i t was ob t a ined a f t e r the trauma o f opening the abdomen. Bo th Hahn e t a l . (191+2) and Delorme e t a l . (1952) have s t a t e d 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 the mix ing curves 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 2 l a b e l l e d r ed c e l l s , c o r r e c t e d counts o f a c t i v i t y be ing ob t a ined b y 2 m l . samples o f b l o o d withdrawn a t the t imes shown. M i x i n g i s b a r e l y complete i n 5 minu tes . 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 not remain cons tan t b u t shows a p e r s i s t e n t s teady d e c l i n e as has been found by o the 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 con- t r a d i s t i n c t i o n to Delorme e t a l . - ( l 9 5 l ) . 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 of cont inuous r eco rds o f the count ing r a t e employing the end window Geiger counters and a r a t e meter r e c o r d i n g through an E s t e l i n e Angus r e c o r d e r . A g a i n mix ing i s shown . t o be b a r e l y complete i n 5 minu tes . 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 s e q u e s t r a t i o n o f 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 , m i x i n g o f 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 the sys temic c i r c u l a t i n g b l o o d i s s lowed, due t o the reduced c a r d i a c output and reduced b l o o d f l o w . F i g u r e IV 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 the sys temic 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 a f t e r 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 exper iments . 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 the p o r t a l v e i n was l i g a t e d . A g a i n , m i x i n g i s b a r e l y complete a f t e r $ minutes , bu t the coun t ing r a t e s t a r t s t o f a l l b y the t e n t h minu te . I t i s d u r i n g t h i s sho r t p e r i o d t h a t i t i s necessary t o withdraw the b l o o d t o a v o i d the e r r o r - on t he one hand, o f incomple te m i x i n g ; on the o the r , o f the d e c l i n e i n the count ing ra te 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 the sp l anchn ic v a s c u l a r bed and the n o r m a l l y o c c u r r i n g decrease i n coun t ing 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 de t e rmina t ion was made i n t o the i n f e r i o r vena cava and the sys temic sample taken from the f emora l a r t e r y i n o rder t o at tempt to 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 by incomple te mix ing w i l l be such t h a t d i l u t i o n w i l l no t be completed, and thus too low a va lue 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 to be g rea t e r i n the second b l o o d volume e s t i m a t i o n than i n the f i r s t , the va lues ob ta ined f o r the 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 too 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 the o c c l u s i o n o f the p o r t a l v e i n du r ing the p e r i o d o f the b l o o d pressure p l a t e a u and about midway i n the t ime o f s u r v i v a l . Though b l o o d con t inued to be l o s t i n t o the bowel , t h i s was t o some ex ten t o f f s e t by the r e t u r n o f b l o o d from the sp l anchn ic bed as the a r t e r i a l p ressure d e c l i n e d p r i o r t o dea th , and p o s s i b l y by plasma re tu rned from the bowel b y the l y m p h a t i c s . These experiments have shown t h a t 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 f o l l o w i n g sudden and acute 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 the o r i g i n a l volume, bu t t h i s va lue cannot be compared w i t h those ob ta ined b y Elman and Co le (1932) o r Boyce and o thers (1935). The i r va lues 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 the sp l anchn i c v a s c u l a r bed and i g n o r e d t h a t p o r t i o n no rma l ly con t a ined w i t h i n the v e s s e l s o f the b e d . An experiment s i m i l a r i n de s ign to the one de sc r i bed i n t h i s t h e s i s was performed by M a l l e t - G u y , Devic and Gangolphe (1950). Unfortunately they chose the dye method t o es t imate the b l o o d volume. Th i s meant t ha t U8 hours had to e lapse between the f i r s t and second b l o o d volume est imations^ t o a l l o w the dye o f the f i r s t e s t i m a t i o n t o d i sappear , though even t h i s was p robab ly not long enough. Because they c o u l d not f i n d t h i o c y a n a t e , subtosan or methylene b l u e i n the 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 a f t e r p o r t a l v e i n l i g a t i o n , they i g n o r e d the c o l l a t e r a l p a t h s . But t h i s i s no t j u s t i f i e d . Moreover, they made no mention 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 dur ing the second e s t i m a t i o n . F i n a l l y , the va lue they ob t a ined 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 not comparable t o t h a t o f Elman and Cole (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 no rma l ly p resen t i n the s p l a n c h n i c v a s c u l a r b e d . The comparable f i g u r e i s 36.7$ as w i l l be seen l a t e r . In order t o d i s c o v e r whether consecu t ive e s t ima t ions o f b l o o d volume c o u l d be made u s i n g the P32 method, two experiments were c a r r i e d ou t , and the r e s u l t s are found i n Table V . I n the f i r s t exper iment , the second de t e rmina t i on f o l l o w e d immedia te ly a f t e r the f i r s t , the t h i r d 30 minutes a f t e r the second. 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 the second exper iment , the second de t e rmina t ion f o l l o w e d immedia te ly - 3 6 - a f t e r the f i r s t and the 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 Sp lanchnic B l o o d Volume The r e s u l t s are shown i n Table V I . The c i r c u l a t i n g b l o o d volume i n these 10 dogs was 8 l . l ( - 17,h) m l . per k g . compared t o the p r ev ious f i g u r e o f 76.9 (£ 6.55) m l . pe r k g . The sp l anchn ic b l o o d volume, t h a t i s , the b l o o d con ta ined 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 t o rec tum, toge ther w i t h the sp leen and pancreas , was found to be 17.7 ( - 5.9) m l . pe r k g . body w e i g h t . This r ep resen t s 21.7 ( - 5.5) % o f the c i r c u l a t i n g b l o o d volume. D i s c u s s i o n . Mass l i g a t i o n o f the oesophagus w i l l occlude the main anastomosis between the sys temic and p o r t a l venous systems, bu t p r o v i d e d the p o r t a l v e i n i s not obs t ruc t ed , i t w i l l no t l e a d to i n c r e a s e d p o o l i n g o f b l o o d w i t h i n the v i s c e r a . L i g a t i o n o f the lower rectum i n t e r r u p t s even fewer anastomoses, and l i g a t i o n o f the l e s s e r mesenter ic a r t e r y p robab ly reduces the i n f l o w by v e r y l i t t l e i n p r o p o r t i o n t o the g rea t amount o f a r t e r i a l 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 . The s p l e e n i n these dogs remained remarkably cons tan t i n s i z e p r o v i d e d t h a t gross man ipu l a t i on was avo ided , p robab ly 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 anaes thes i a , though u n - doubtedly 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 to dog. I t i s easy t o a p p l y the 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 imu l t aneous ly so tha t the er rors o f uncompensated dra inage by the p o r t a l o u t l e t , or c o n - g e s t i o n from o b s t r u c t i o n to the p o r t a l o u t l e t can be a v o i d e d . Removal o f the i n t e s t i n e s i s p o s s i b l e w i t h o u t any escape o f the con ta ined b l o o d . - 37 - The o n l y o ther comparable f i g u r e s are those produced by 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 i so tope may be m o d i f i e d t o measure the volume o f a p a r t o f the c i r c u l a t i o n by e x c l u d i n g t h a t p a r t from the g e n e r a l c i r c u l a t i o n immedia te ly be fo re the i n j e c t i o n o f l a b e l l e d c o r p u s c l e s ( N y l i n - 191+7). The b l o o d volume so measured, i s the t o t a l b l o o d volume l e s s t h a t o f the exc luded s e c t i o n . When the exc luded a rea i s opened, the b l o o d i n wh ich there are no l a b e l l e d co rpusc l e s mixes w i t h and d i l u t e s the r a d i o a c t i v e b l o o d i n the g e n e r a l c i r c u l a t i o n . Th i s d i l u t i o n i s a matter o f the volume o f the exc luded sect ion! ' I n t h e i r experiments the sp l a nc h n i c bed was taken as stomach, i n t e s t i n e s , s p l e e n , pancreas and l i v e r . This was e s t ima ted to c o n t a i n between 20$ and 50$ o f the 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$. Whi l e t h i s method has the advantage o f not r e q u i r i n g the e v i s c e r a t i o n of the dog, i t i s sub jec t t o the s e r i o u s e r r o r o f the escape o f l a b e l l e d r e d c e l l s i n t o the exc luded area by anastomotic channe l s . I n a d d i t i o n , i t i s i m p o s s i b l e s imu l t aneous ly t o clamp bo th the f eed ing and d r a i n i n g v e s s e l s o f the c o n s t i t u e n t components o f t h e i r sp l anchn ic v a s c u l a r bed , and thus a con- s i d e r a b l e e r r o r from e i t h e r conges t ion o r emptying o f the v e s s e l s w i l l o c c u r . I n three animals they es t ima ted the volume i n the "proper hepa t i c supp ly" t o be 16, 6 and 22$ o f t h e i r sp l anchn ic b l o o d volume. In these th ree dogs, t h e i r sp l a nc hn 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$. Therefore , b y s u b t r a c t i n g the "proper h e p a t i c supp ly" from t h e i r sp l anchn i c b l o o d volume, f i g u r e s cor responding to our s p l a n c h n i c b l o o d volume are 1+1, 23 and 19$ r e s p e c t i v e l y . - 38 - I f the b l o o d volume o f the dog i s taken as 76.9 m l / k g body weight and the b l o o d volume o f the s p l a n c h n i c v a s c u l a r bed i s 17 .7 m l / k g body we igh t , t hen a f t e r the sp l a nc hn i c v a s c u l a r bed has been exc luded , the c a p a c i t y o f t h e remain ing sys temic v a s c u l a r bed i s 59.2 m l / k g body we igh t . 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 the sys temic c i r c u l a t i n g b l o o d volume i s reduced to 32.7 m l / k g body w e i g h t . I t can be argued t h a t the t r ue 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 he re fo re t he d i f f e r e n c e between t h i s f i g u r e and the 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 t h the s p l a n c h n i c bed e x c l u d e d , (59.2 m l / k g ) , t h a t i s , 26 .4 m l / k g body weigh t or 4 4 . 6 $ , f o r the remain ing 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 a v a s c u l a r bed reduced by the normal c a p a c i t y o f the s p l a n c h n i c bed . I t i s t h i s f i g u r e which corresponds t o t h a t o f Elman & Cole (1932) . 4 . Haematocr i t E s t i m a t i o n s Tab le V I I shows haematocr i t r e s u l t s ob ta ined 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 . D i s c u s s i o n . The d i f f e r e n c e i n the haematocr i t v a l u e s f o r b l o o d drawn from the femora l v e i n before anaes thes ia w i t h sodium p e n t o b a r b i t a l , and from the femora l a r t e r y f o l l o w i n g anaes thes ia are o f d o u b t f u l s i g n i f i c a n c e (p<^0.05) . I t i s not p o s s i b l e t o say which o f the two v a r i a b l e s ( the source o f the b l o o d or the p e n t o b a r b i t a l anaes thes ia ) i s the cause. T h i r t y minutes and 40 minutes a f t e r o c c l u s i o n of the p o r t a l v e i n , the haematocr i t va lue s w i t h i n the a r t e r i a l system are seen to have f a l l e n i n every case except 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 haematocr i t v a l u e s of the b l o o d w i t h i n the p o r t a l v e i n are seen to 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 ex ten t (p ^ 0 . 0 1 ) . The l a t t e r r e f l e c t s a cont inued escape o f plasma i n t o the bowel w a l l . The cause o f the con t inued f a l l i n the a r t e r i a l haematocr i t s i s harder t o account f o r . I t i s p e r t i n e n t a t t h i s p o i n t t o d i s c u s s 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 . Ingraham e t a l . (1950) s t a t e d t ha t p e n t o b a r b i t a l anaes thes ia i n t w o - t h i r d s of the dose n o r m a l l y used (21.4 mg/ kg body weigh t ) has no e f f e c t on the course o f events i n haemorrhagic shock, bu t i t does , n e v e r t h e l e s s , cause enlargement o f the s p l e e n , produce h a e m o d i l u t i o n , and cause conges t ion o f the v i s c e r a (Wiggers - 1942) . These obse rva t ions have been supported by Wang and Walco t t (1952) who found there 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 p e n t o b a r b i t a l anaes the s i a , and by Bol lman e t a l . (1938) , Hahn e t a l . (1942) and C o u r t i c e and Gunton (1949) , a l l o f whom found t ha t the sp leen was en l a rged 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 ached l e a d shots t o the s p l e e n , and by x - r a y observed i t s enlargement 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 . I n order t o see whether splenectomy would have any e f f e c t on the course o f events 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 , fou r experiments were done. I n two, the abdomen was opened, the 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 the 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 the sp leen had shrunk, the s p l e n i c p e d i c l e was clamped and the sp leen exc luded from the c i r c u l a t i o n . The p o r t a l v e i n was then l i g a t e d and the dogs d i e d i n 56 minutes and 72 minutes r e s p e c t i v e l y , w i t h no change i n the course o r i n the pos t mortem appearance of the i n t e s t i n e s . The b l o o d pressure f e l l , a f t e r l i g a t i o n , t o a l e v e l o f between - 40 - 80-90 mm. Hg over t en minutes , and then d e c l i n e d s l o w l y u n t i l a p ressure o f 30-40 mm. Hg was reached . I n the t h i r d and f o u r t h exper iments , the decrease 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 p o r t a l v e i n l i g a t i o n , bu t w i t h the sp leen removed (Table V I I I ) . B o t h these dogs showed a g rea te 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 the mesentery than those w i t h o u t splenectomy. However, t h e i r course was u n i n f l u e n c e d , and the decrease 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 those dogs w i thou t splenectomy. I n e f f e c t , the sp l anchn i c v a s c u l a r bed seems to 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 not 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 sp l een i n dogs has not been r e c o r d e d . T h i s i n d i c a t e s t h a t whatever the 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 the 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 course o f even t s , f o r the re can be no g rea te r s t i m u l u s t o s p l e n i c enlargement than a r i s e i n p o r t a l venous p r e s su re , nor decrease i n the s p l e n i c volume than t o t a l r e m o v a l . The e f f e c t o f p e n t o b a r b i t a l anaes thes i a on p e r i p h e r a l haemato- c r i t s i s harder t o e v a l u a t e . The gene ra l e f f e c t i s t o produce an immediate haemodi lu t ion wh ich con t inues unchanged f o r s e v e r a l hours (Bol lman e t a l 1938, Wiggers 1942, C o u r t i c e and Gunton 1949) . I f however the experiments con t inue f o r too l o n g , haemoconcentrat ion w i l l o ccu r , due t o dehydra t ion o f the an imal (Seavers and P r i c e 1949) . I f haemorrhage o c c u r s , haemo- d i l u t i o n i s p reven ted , f o r dogs under p e n t o b a r b i t a l anaes thes ia r e s t o r e no p a r t o f the plasma l o s t b y haemorrhage, p robab ly because o f a r t e r i o l a r r e l a x a t i o n wh ich 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 the 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 the sp leen as a b l o o d s torage 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 haemorrhage i s now u s u a l l y d i s coun ted ( C o u r t i c e and Gunton 1949, Gibson e t a l . 1946, Delorme e t a l . 1952) . F u r t h e r , haematocr i t v a l u e s are known to v a r y w i d e l y w i t h the source o f the b l o o d used . For t h i s r eason , 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 the f a l l o f haematocr i t va lues recorded he re , bu 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 the r e t u r n to the c i r c u l a t i o n o f plasma from the i n t e s t i n e s th rough the l ympha t i c system. 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 t r i b u t a r i e s . Dog No. 1 Weight 9 .1 k g . 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 through the muscle l a y e r t o i t s t e r m i n a t i o n , a sho r t d i s t a n c e from the anus . No p e l v i c sys temic v e i n s con ta ined l a t e x . 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 , which r a n from the mesentery to the f a s c i a o v e r l y i n g the k i d n e y . From the 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 branches which r a n w i t h the two v a g i ne rves , and d r a i n e d i n t o the sys temic 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 ther p o r t o - s y s t e m i c anastomoses c o u l d be found. Dog No. 2 Weight 15.9 k g . Male A s m a l l branch r an a n t e r i o r l y from the rectum i n the r e f l e c t i o n o f per i toneum onto the p o s t e r i o r surface o f the p r o s t a t e , and thence i n t o a v e i n which 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 abdominal w a l l . A few t i n y venu les c o u l d be seen runn ing i n the mesentery o f the rectum, bu t no o ther 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 the mesentery o f the 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. diameter) wh ich 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 sup ra r ena 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 vena cava 1 cm. above the r i g h t r e n a l v e i n . A t the c a r d i a , s m a l l g a s t r i c branches amalgamated to form main branches wh ich accompanied the two vagus ne rves . From the se , t h ree branches 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 lowes t 5 cm. o f the oesophagus. (See F i g u r e Dog No. 3 Weight 15 .0 k g . Male Three cms. from the anus on the l e f t s i d e , a l a t e x f i l l e d v e i n (0 .4 mm. d iameter ) 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 the 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 a n t e r i o r aspec t o f the rec tum, a l a t e x f i l l e d v e i n r a n i n the p e r i t o n e a l r e f l e c t i o n t o the p o s t e r i o r aspect o f the p r o s t a t e . T h i s v e i n was j o i n e d by a s m a l l v e i n i n the mesentery. A t the upper rectum th ree s m a l l v e i n s (0 .3 mm. or l e s s i n d iameter) r a n from the 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 an from the duodenal mesentery to j o i n the l e f t lumbo-adrenal v e i n , but t h i s v e i n had o n l y t r a c e s o f l a t e x w i t h i n i t . A long the r i g h t "vagus a v e i n r a n connec t ing the v e i n s o f the c a r d i a w i t h those o f the lower oesophagus and o f the 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. A long the l e f t vagus , a v e i n r a n connec t ing w i t h the lower oesophageal - 43 - v e i n s , bu t not anastomosing w i t h the v e i n s o f the p o s t e r i o r t h o r a c i c w a l l . (See F i g u r e V b) Dogs No. At tempts t o d i s p l a y anastomoses by u s i n g radio-opaque media 4 & 5 f a i l e d , o n l y the main p o r t a l venous t r i b u t a r i e s f i l l i n g . D i s c u s s i o n : 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 venu les was o b t a i n e d , show t h a t i n the dog, the main p o r t o - s y s t e m i c venous anastomoses occur a t the lower end o f the oesophagus, connec t ing the g a s t r i c p o r t a l v e i n s t o the oesophageal sys temic v e i n s , i n r e l a t i o n t o the r i g h t and l e f t vagus n e r v e s . Two o ther groups o f anastomoses o c c u r , bu t o f a r e l a t i v e l y minor degree , those i n the mesentery running t o the l e f t lumbo-adrenal v e i n , and those connec t ing the lower rectum w i t h the p r o s t a t i c v e i n s . These f i n d i n g s a re supported by the coun t ing r a t e s obra ined i n the p o r t a l venous b l o o d when the lower oesophagus and i t s v e i n s are occ luded (see Table I I I ) . Without o c c l u s i o n , the p o r t a l venous count r i s e s t o a much g rea te r ex ten 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 sys temic v e i n , than when the oesophagus i s l i g a t e d . I n the l a t t e r case the r i s e can be accounted f o r by the l e a k o f plasma i n t o the b o w e l . 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 sys temic 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 por tosys temic venous anastomoses save i n man. B u t l e r (1S51) i n an i n v e s t i g a t i o n o f the ve ins 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 comitantes o f the vagus ne rve , j o i n i n g the l e f t g a s t r i c v e i n s t o the 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 ne tworks . - 4 4 - Wermuth (1939) i n v e s t i g a t i n g the anastomoses a t the o ther end o f the 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 rectum to an h y p o g a s t r i c v e i n on e i t h e r s i d e , b ) d o r s o v e n t r a l , from the rectum a t a lower l e v e l than a) t o the s ide o f the u terus* Edwards (1951) by u s i n g a bar ium su lpha te suspens ion i n j e c t e d i n t o the femora l v e i n s i n th ree normal s u b j e c t s , confirmed a d e s c r i p t i o n by Schmiedel ( 1 7 4 4 ) ; namely, t h a t two main groups o c c u r r e d . 1) Normal m u l t i p l e f i n e v e s s e l s above the rectum and i n the r e t r o p e r i t o n e a l areas o f the abdomen 2) Abnormal communications between the p o r t a l and sys temic systems, e . g . t e r m i n a t i o n of the 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 the re a re no c l e a r - c u t d e s c r i p t i o n s o f the normal v e s s e l s . I n the presence o f p o r t a l h y p e r t e n s i o n , there are numerous a r t i c l e s concern ing the s i t u a t i o n o f d i l a t e d por tosys temic anastomotic and c o l l a t e r a l v e i n s (Sappey 1883, Hclndoe 1928) wh ich a l s o develop 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 e t a l . (1951) remarked on the w e l l marked p e l v i c por tosys temic 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 t h a t o f man. 6. E x h i b i t i o n o f a n t i b i o t i c s S i x experiments were performed, i n th ree o f which the a n t i b i o t i c 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 , i n th ree f o l l o w i n g l i g a t i o n . The method o f l iga t i r fg 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 d e s c r i b e d . Continuous records o f sys temic a r t e r i a l b l o o d pressure were - 4 5 - o b t a i n e d . 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 emora l v e i n j the aureomycin was g iven by mouth by 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 these 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 l i g a t i o n ( i ) Female. Weight 25.0 k g . 500,000 u n i t s o f p e n i c i l l i n g i v e n 1 hour p r i o r t o l i g a t i o n . Dog d i e d 50 minutes f o l l o w i n g l i g a t i o n , w i thou t a l t e r a t i o n i n i t s cour se . ( i i ) M a l e . Weight 7 .5 k g . 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§- hour s , 3 § hours and h a l f an hour before l i g a t i o n . Death i n 65 minutes f o l l o w i n g l i g a t i o n , course u n a l t e r e d . ( i i i ) Female . Weight 23.2 k g . 250 mgm. aureomycin g i v e n i n three doses (10 a . m . , 1 p .m. and 4 p .m. ) on day b e f o r e , th ree 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 minutes a f t e r the l a s t dose . The dog d i e d 73 minutes l a t e r , w i t h u n a l t e r e d cour se . (b) A n t i b i o t i c g i v e n a f t e r l i g a t i o n ( i ) M a l e . Weight 20.4 k g . 500,000 u n i t s of p e n i c i l l i n 10 minutes a f t e r l i g a t i o n . Death i n 100 minutes , course u n a l t e r e d . ( i i ) M a l e . Weight 15.9 k g . 500,000 u n i t s o f p e n i c i l l i n 9 minutes a f t e r l i g a t i o n . Death i n 32 minutes , course u n a l t e r e d . ( i i i ) M a l e . Weight 12.2 k g . 500,000 u n i t s o f p e n i c i l l i n 5 minutes a f t e r l i g a t i o n . D i e d i n 114 minu tes . Course u n a l t e r e d . D i s c u s s i o n : F o l l o w i n g the obse rva t ions o f Markowitz e t a l . ( IS49) on the a b i l i t y o f p e n i c i l l i n t o 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 a r t e r y l i g a t i o n , these experiments were c a r r i e d o u t . 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 the p o r t a l v e i n , whether g i v e n before or a f t e r l i g a t i o n . I t was thought t h a t perhaps the a n t i b i o t i c s i n q u e s t i o n might be u n a v a i l i n g a g a i n s t the organisms and t h a t f u r t h e r work should be done t o i n v e s t i g a t e the normal b a c t e r i a l f l o r a o f the dog ' 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 a n t i b i o t i c s . T h i s work has not been completed. GENERAL DISCUSSION These experiments have shown t h a t the average r e d u c t i o n i n c i r c u l a t i n g b lood 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) o f 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 h ighe r than t ha t o f M a l l e t - G u y e t a l . (1950) , but i f comparable volumes are t a k e n , t h a t i s , i f the b l o o d no rma l ly present w i t h i n the sp l anchn ic c i r c u l a t i o n i s sub t r ac t ed from the volume seques t ra ted a f t e r l i g a t i o n , then the r e s u l t i n g f i g u r e , 44 .8$ , i s midway between t h a t o f Elman a n d Cole 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 which i s r e q u i r e d to 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 ha t no f i g u r e i s u s e f u l (Huizenga e t a l . 1943) . 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 pas t (see Tab le IX a ) . These have l i t t l e comparable va lue f o r the method o f de te rmin ing them was so v a r i a b l e . Of much more v a l u e a re the f i g u r e s ob ta ined by b l e e d i n g to 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 Tab le I X b ) . A g a i n , comparison i s d i f f i c u l t f o r the l e v e l s of shock b l o o d pressure d i f f e r e d . I n genera l the procedure o f Wiggers e t a l . (1946) was used . I n t h i s , b l e e d i n g (a t a r a t e o f around 40 m l / k i l o body weight /min) con t inued u n t i l the b l o o d - 47 - p ressure f e l l t o a l e v e l o f 50 mm. H g . , a t which l e v e l i t was main ta ined f o r 90 minu tes , 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 pressure t o 30 mm. Hg. f o r 45 minutes more. I f these amounts are compared to the r e s u l t s of the present experiments (43 .1 - 73.2 m l / k g , average 5 7 . 9 ) , the l a t t e r are g e n e r a l l y h i g h e r . The t imes o f s u r v i v a l are however s h o r t e r . The de t e rmina t ions were made 30 - 40 minutes a f t e r o c c l u s i o n , and oundoubtedly f u r t h e r decrease i n the c i r c u l a t i n g b l o o d volume must have occur red be fo re dea th . Therefore an adequate e x p l a n a t i o n o f the cause of death a f t e r 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 ncompa t ib l e w i t h an adequate c a r d i a c output to s u s t a i n l i f e . However, the i n e v i t a b i l i t y o f death af ter- p o r t a l v e i n o c c l u s i o n con t r a s t ed w i t h the 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 such l e v e l s , and the f a c t t h a t the t o t a l v a s c u l a r bed has been reduced by the e x c l u s i o n o f the sp l anchn i c p o r t i o n (17.7 m l / k g ) so t ha 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 to serve a s m a l l e r v a s c u l a r a rea suggest tha t o ther f a c t o r s are i m p l i c a t e d . An analogy may make t h i s c l e a r . I f b o t h l e g s are amputated, the con ta ined b l o o d , which 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 lood volume was 1,000 m l . , then the new b lood volume i s 840 m l . But t h i s volume i s r e q u i r e d t o serve a v a s c u l a r bed which has been reduced by 160 m l . Therefore the r a t i o o f c i r c u l a t i n g b l o o d to v a s c u l a r bed has not been a l t e r e d . I f now b l e e d i n g o c c u r s , and the c i r c u l a t i n g b l o o d volume i s found to be 500 m l , , then 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 not 50%, but the d i f f e r e n c e between the pos t b l e e d i n g b lood volume, and the pos t amputat ion b l o o d volume, namely 340 m l , , o r expressed as a - 48 - percentage 340 x l Q Q m 4 0 . 5 $ . 840 I f the sp l a nc hn i c v i s c e r a are cons ide red t o be the amputated l e g s , and the l o s s o f b l o o d i n t o the sp l anchn ic bed to be the pos t amputat ion b l e e d i n g , then the t r ue 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 the dog ' s weight to be 10 k g . , can be worked ou 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 con ta ined w i t h i n m 177 m i > the s p l a n c h n i c v i s c e r a . * . C a p a c i t y o f reduced v a s c u l a r a rea = 592 m l . Pos 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 . , or expressed as a % 265 - , n n m 44 .8$ 5 9 2 T h i s must be a s s o c i a t e d w i t h the reduced p o r t a l b l o o d supply t o the l i v e r . T h i s may produce ( i ) a decrease i n the oxygen supp ly t o the l i v e r , ( i i ) a decrease 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 i i ) a t o x i n produced i n the 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 not n e c e s s a r i l y exclude such a t o x i n . L i v e r r e g e n e r a t i o n i s not dependent on p o r t a l venous b l o o d . Dogs w i t h Eck f i s t u l a e s u r v i v e w i thou t d e t e c t a b l e d i f f e r e n c e 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 h e a l t h . However, i n such dogs, any p o r t a l component can reach the l i v e r e v e n t u a l l y by the hepa t i c a r t e r y ; 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 hypoxia i s known t o occur i n shock (Enge l e t a l . 1943, 1944) . S u r v i v a l of dogs f o l l o w i n g b l e e d i n g to o therwise i r r e v e r s i b l e shock l e v e l s can be ob ta ined i f the oxygen supp ly t o the l i v e r i s supplemented (Frank e t a l . 1946, Delorme 1951) . L i g a t i o n of the p o r t a l v e i n w i l l cause hypox ia 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 the oxygen c a r r i e d by the p o r t a l venous b l o o d . Though the h e p a t i c a r t e r y i s the dominant source o f oxygen ( B a r c r o f t and Shore 1912, B l a l o c k and Mason 1936) , the p o r t a l venous b l o o d does supp ly a s u b s t a n t i a l p o r t i o n o f the oxygen r e q u i r e d (Smythe e t a l . 1951) . 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 , the h e p a t i c a r t e r y f l o w r i s e s (Schwiegk 1932, G r i n d l a y e t a l . 1941, Sance t t a 1953) , thereby i n c r e a s i n g the t o t a l oxygen s u p p l i e d by t h i s sou rce . T h i s would compensate i f the h e p a t i c a r t e r y supply d i d not i t s e l f d e c l i n e due to the d e c l i n e i n c a r d i a c ou tpu t . I f l i g a t i o n i s i ncomple t e , when the c i r c u l a t i n g b l o o d volume i s augmented by t he escape o f p o r t a l b l o o d back i n t o the sys temic c i r c u l a t i o n , or i f the c i r c u l a t i n g b l o o d volume i s ma in ta ined by t r a n s f u s i o n , the f l o w w i t h i n the h e p a t i c a r t e r y i s p robab ly main ta ined 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 the 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 the p o r t a l v e i n , postpones death and a l l o w s s u r v i v a l 4 hours (Elman and Cole 1934) . L i g a t i o n o f the sp l anchn ic 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 death (Boyce e t a l . 1935) . Simultaneous 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 p o r t a l v e i n has not been i n v e s t i g a t e d . I n two dogs the r i g h t femora l a r t e r y was connected t o the p o r t a l v e i n on the h e p a t i c s ide o f the l i g a t u r e , i n an attempt t o a u t o - v i v i - perfuse the l i v e r . These dogs l i v e d 105 and 146 minutes , but no a l t e r a t i o n i n t h e i r course was seen. 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 ressure was m a i n t a i n e d , there would be a g rea te r escape o f b l o o d i n t o the s p l a n c h n i c b e d . T h i s v a s c u l a r bed would 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 put i n t o i t b y the f eed ing a r t e r i e s . There are no r e s u l t s a v a i l a b l e o f measurements o f the ex ten t of the h y p o x i a o f the l i v e r or o f the amount o f the decrease i n f l o w o f the h e p a t i c a r t e r y f o l l o w i n g p o r t a l v e i n l i g a t i o n . F u r t h e r i n v e s t i g a t i o n o f these p o i n t s i s i n d i c a t e d . The p r e l i m i n a r y experiments were made u s i n g i n t e r m i t t e n t p o s i t i v e p res su re oxygena t ion 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 imes were 50, 70 , 56, and 86 minutes , average 65.5 minu tes . I t does no t appear tha t any advantage i s gained by r e s p i r a t i o n o f pure oxygen. I n haemorrhagic shock, i f the p o r t a l venous pressure i s reduced, then a much g r ea t e r decrease occurs i n the p o r t a l venous f l o w , than i s the case w i t h a comparable f a l l i n sys temic a r t e r i a l p ressure and the hepa t i c a r t e r i a l flcwQ (Wiggins e t a l . 1946) . T h i s was confirmed by 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 to a l e v e l o f 40 mm. Hg. They found t h a t the prehaemorrhage f low o f 26 .0 m l / m i n / k g body weight was reduced t o 3.7 m l / m i n / k g . N e v e r t h e l e s s , t he re appears t o be an attempt to m a i n t a i n p o r t a l f l o w a t the expense o f the supply t o the p o s t e r i o r h a l f o f the body ( B l a l o c k and Levy 1937) . - 5 i - These obse rva t ions do not e x p l a i n what d e l e t e r i o u s process f o l l o w s hypox ia o f the l i v e r . Two hypotheses are proposed p r e s e n t l y . Shor r e t a l . ( l ° 5 l ) have p o s t u l a t e d the occurrence o f a vasodepressor 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 , which i s produced i n the hypoxic l i v e r , and which can be shown t o i n h i b i t the e f f e c t o f neo- synephr ine on the meta a r t e r i o l e s o f the r a t meso-appendix. Frank e t a l . (1952) by obse rv ing the e f f e c t i v e n e s s o f aureomycin i n i n c r e a s i n g the s u r v i v a l f o l l o w i n g haemorrhagic shock (b l eed ing t o 30 mm. Hg.) p o s t u l a t e t ha t death from t r aumat i c shock i n which the 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 anaerobic b a c t e r i a l o r i g i n . H i s manner o f g i v i n g aureomycin was t o admin i s t e r 2.5 gm. tw ice 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 ee o f £ . c o l i and C l o s t r i d i a , which u s u a l l y took 6 d ays . Compared w i t h a c o n t r o l group, 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 dosage. I f 5 gms. were g i v e n , o n l y 3-5 hours before b l e e d i n g , h$% s u r v i v e d . P e n i c i l l i n was unable t o i n f l u e n c e the course o f e v e n t s . The organism r e s p o n s i b l e was no t d i s c l o s e d . But Hardy e t a l . (195U) were unable t o s u b s t a n t i a t e the work o f Frank e t a l . , and Ne lson (195U) found an i d e n t i c a l i n c i d e n c e o f p o s i t i v e b l o o d c u l t u r e s i n shocked dogs and i n c o n t r o l s . The p resen t experiments have not p r o p e r l y i n v e s t i g a t e d the e f f e c t o f a n t i b i o t i c s . A l l t h a t can be s a i d i s t ha t i n the doses g i v e n the course i s not i n f l u e n c e d . These experiments shou ld be f u r t h e r pursued. - 52 - S U M M A R Y A review of the literature on ligation of the portal vein has been presented. A brief survey of the literature on the ligation of the hepatic veins and the hepatic artery has been included. The review reveals that while there is no disagreement that the result of sudden acute ligation of the portal vein in dogs is inevitably death, there is dis- agreement as to the cause of death. The main theories are (i) that exsanguination into the splanchnic vascular bed occurs, (ii) that the loss of blood is insufficient to cause death, and that other factors must be implicated, the "toxic" theory. The species difference in the effects of ligation appears to l i e in the degree of porto-systemic venous anastomoses. The experiments described in this thesis were performed with the dog as the experimental animal. A measurement of the decrease in circu- lating blood volume following ligation of the portal vein, using the "labelled" red ce l l method, was made. With 11 dogs, 30 minutes after portal vein ligation, the decrease amounted to 57.9$ 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 ce 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 in the systemic arterial haematocrit, and rise in the portal venous haematocrit. By the in- jection of latex into the portal vein of 3 dogs, the main porto- systemic venous anastomoses were found to occur in 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 anti- biotics under the conditions of the experiments. TABLE I S u r v i v a l Times (mins . ) 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 Oesophageal Vesse l s No. Occluded 1 75 2 59 3 46 4 54 5 53 6 52 7 58 8 61 9 48 10 63 11 47 Dog No Oesophageal No. L i g a t u r e 12 50 13 70 14 56 15 85 16 95 17 89 18 95 19 77 20 47 21 74 22 95 23 85 24 85 25 113 Dog No Oesophageal L i g a t u r e No. Hepar in - 10 mgs/kg 26 124 27 90 28 93 29 61 30 110 31 55 32 67 33 102 34 95 Average w i t h 56.0 + 8 . 5 c a l c u l a t e d s tandard d e v i a t i o n . 79.7 * 18.9 88.6 t 23.26 TABLE II Dog Sex Wt. P r e l i g a t i o n c i r c u l a t i n g (kg) blood volume standard deviation Reduction i n C i r c u l a t i n g Blood Volume P o s t - l i g a t i o n c i r c u l a t i n g blood volume Reduction of c i r c u l a t i n g blood volume (ml) (ml/kg) (ml) (ml/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 Average with calculated 13.6 1045 76.9+ 6.56 462 32.7* 8.23 57.9* 8.77 .TABLE I I I True Count ing Rates i n C / S / l O m l . f o r Sys temic 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 B lood P o r t a l Venous Blood 28-31 mins . 5 m i n s . a f t e r 28-31 m i n s . 5 m i n s . a f t e r * a f t e r o c c l u s i o n % 2nd i n j e c t i o n % a f t e r o c c l u s i o n % 2nd i n j e c t i o n 5 m ins . a f t e r o f p o r t a l v e i n column 2 i s (36-41 m i n s . a f t e r column 4 i s o f p o r t a l v e i n column 6 i s (36-41 m i n s . a f t e r column 8 i s Pog 1 s t i n j e c t i o n (background) o f column 1 p . v . o c c l u s i o n ) o f column 2 (background) o f column 1 p . v . o c c l u s i o n ) o f column 6 (1) (2) (3) (4) (5) (6) (7) (8) (9) 1 136 .0 132.3 97.3 293-9 222.1 156.6 115 .1 153-8 98.2 2 58 .0 42 .0 92.4 101.4 241-7 72.5 125 .0 73-4 101.3 3 651.1 507-8 77.9 1669.1 328.7 622.6 95.6 647-7 104.0 4 140.4 133.9 95.4 372.0 277.9 196.9 140-3 203-8 103-5 5 60.8 47.1 77-5 157.7 334.8 83-3 137.0 83-8 100.7 6 304-5 258.5 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 93-3 97.9 10 107 .8 87-3 80.9 187-1 214-4 120.8 112 .0 102.0 84-5 11 136.5 117.5 8 6 . 1 409-8 343 .9 191-5 140.3 181.2 94.6 Average w i t h c a l c u l a t e d 85-0 + 13 .8 278.8 + 8 0 . 2 117.2 + 15-9 101.3 +.7.5 s tandard d e v i a t i o n . TABLE IV Estimation of blood volume of dogs, various authors. Author Bonnycastle & Cleghorn (1942) Courtice (1943) Krieger et a l . (1948) Delorme et a l . (1951) HcLain et a l . (1951) Method T-1824 T-1824 T-1824 Iodinated protein P 3 2 P32 Bleeding T-1824 Volume (ml/kg body weight) 82.7 79.0 105.0 94.0 97.0 100.3 62.0 89.0 TABLE V Consecut ive e s t i m a t i o n s o f b l o o d volume 1 s t B l o o d Volume 2nd B l o o d Volume 3rd B l o o d Volume Sex Wt. (kg) de terminat ion , ( m l , ) de t e rmina t ion ( m l . ) de t e rmina t ion ( m l . ) Dog 1. Male 18 .8 1338.0 1380.0 1412.3 Dog 2 . Female 6.8 466.0 452.3 , i TABLE VI Measurement o f Sp l anchn ic Vascu la r B l o o d Volume Dog No. Wt. (kg) Sex C i r c u l a t i n g B l o o d Volume (ml) m l / k g Sp l anchn ic B l o o d Volume (ml) m l / k g 1 5.9 F 393.5 66.7 60.3 10.2 2 6.6 F 650.8 98.6 99 .0 15 .0 3 4 .1 F 472.4 115.2 96.3 23.5 4 5.7 M 337.8 59.3 56.8 10 .0 5 7.3 F 513.9 70.4 103.8 14.2 6 15 .5 F 1299.7 83.9 297.7 19.2 7 6.8 F 612.8 9 0 . 1 . 186.3 27.4 8 17 .1 M 1514.7 88.6 377.1 22 .1 9 18.6 M 1233.5 66.3 253.1 13.6 10 9.6 M 692.4 72 .1 210.0 21.9 Average 9 .7 772.2 81.4117.4 174.0 17.7: % o f C i r c u l a t i n g B l o o d Volume 15.3 15.2 20.4 16 .8 20.2 22.9 30 .4 24.9 20.5 30 .3 21.7*5.5 w i t h c a l c u l a t e d s tandard d e v i a t i o n . TABLE VII Haematocrits Pre- anaesthetic Venous Dog Systemic (1) (2) 1 40 2 43 3 46 4 28 5 40 6 57 7 55 8 52 9 46 10 47 11 43 Post- anaesthetic Arterial Systemic (3) 34 41 45 30 40 56 53 50 44 46 43 Difference (3) - (2) (4) -6 -2 -1 •2 0 -1 -2 -2 -2 -1 0 Mean -1.4 Deviation From Mean (5) 4.6 0.6 0.4 3.4 1.4 0.4 0.6 0.6 0.6 0.4 1.4 Standard deviation - /6(x - x ) 2 n - 1 - / 38.56 10 - 1.96 Standard error of mean - 0.59 t = 1̂ 4 • 2.3 3759 p < 0.05 After 28-31 mins. Arterial Systemic (6) 36 34 45 29 35 55 47 43 40 40 43 Difference (6) - (3) (7) +2 -7 0 -1 -5 -1 -6 -7 -4 -6 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 Mean -3.2 Standard deviation 1 n - 1 - /100.04 10 - 3.16 Standard error of mean « 0.301 t = 5̂ 2 a 1 0 . 6 07301 .' P<0.01 After 36-41 mins. Arterial Systemic (9) Following occlusion of portal vein After 28-31 mins. Portal Difference Venous (10) 60 66 75 48 62 73 72 75 66 65 61 (10) - (3) (11) 26 21 30 18 22 17 19 25 22 19 18 Deviation From Mean (12) 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 Standard deviation - / S ( x - x V n - 1 170.75 10 4.13 Standard error of mean - 1.26 t - . /. p < 0.01 2 1*\ - 17.0 After 36-41 mins. Portal Venous (13) TABLE F i l l Reduction i n circulating blood volume following splenectomy and portal vein ligation Blood volume following splenectomy and portal Weight Blood Volume vein ligation Survival time Dog Sex kg ml ml/kg n i l % reduction mins. 1 M 20.9 1893 90.5 754.7 60.1 68 M 14.1 874 62.0 471.0 46.1 72 TABLE IX Volume o f b l o o d removed to cause " i r r e v e r s i b l e ' 1 shock (a) (b) By b l e e d i n g d e f i n i t e volumes o f b lood By 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 Amount Author Range Average m l / k g m l / k g m l / k g B l a l o c k (1931) 45 Huizenga (1943) 20-56 40.0 Boyce (1935) 58 Ingraham (1950) 49.9 I reneus (1944) 50 Hay (1951) 27 .5 -67 .2 42.9 ° i M a l l e t - G u y (1950) 40 Wang (1952) 48 .8 -71 .5 60.8 Nelson (1954) 52.0 F i g . I Concurrent r e co rd ings o f p o r t a l v e i n b l o o d pressure and sys temic b l o o d p r e s s u r e . F i g . I I M i x i n g o f P 5 2 l a b e l l e d r e d c e l l s i n the gene ra l c i r c u l a t i o n . Mixing of P^2 labelled red cells i n the general circulation. 40 Corrected counts/ 20 Dog I -* Dog II. 6 2 4 6 8 10 20 Tlas (alrmtee) 30 40 F i g . 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 count ing r a t e s . S tandard e r r o r _ 5$ - fe- • Standard e r r o r „ 2% accuracy accuracy F u l l s c a l e meter range " 5 , 0 0 0 coun t s /min . F i g . IV (a) M i x i n g o f P™ l a b e l l e d r e d c e l l s i n gene ra l c i r c u l a t i o n 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 portal TO In ligation. Dog I. -Ma 10 15 F i g . IV (b) M i x i n g o f P 3 2 l a b e l l e d red c e l l s i n gene ra l 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 count ing r a t e s - 6 8 - 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 . Main anastomotic v e i n accompanying L . vagus nerve Small venule running i n mesentery of duodenum - 69 - F i g . V (b) Dog 3. Portal venous t r i b u t a r i e s injected with latex. 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 vein 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 . Intravenous A n a e s t h e s i a . New Y o r k , P a u l B . Hoeber, I n c . 19kh. 2. Adelman, M . H . , Megibow, S . J . & Blum, L . A Method o f Automat ic C o n t r o l l e d R e s p i r a t i o n f o r Anaes thes i a i n the Dog. Surgery - 28 s 101*0, December 1900. 3 . Andrews, E . & H r d i n a , L . The Cause o f Death i n L i v e r A u t o l y s i s . S u r g . , G y n . , Obs t . - 52: 6 l , 1931 U. A r s t , D . B . , S i l v e r , M . & Lahey, W . J . The Use o f V i n y l P l a s t i c Tubing i n Recording Pressure Phenomenon. Am. Hear t J . - hZ} 7U6, 1951. 5. B a r c r o f t , J . & Shore, L . E . Gaseous Metabol ism o f L i v e r - i n f a s t i n g and l a t e d i g e s t i o n . J . P h y s i o l o g y - i £ : 296, 1912. 6. B a r t l e t t , F . K . , Cooper, H . J . & Long, E . R . The Independence o f the Lobes o f the L i v e r . Amer. J . P h y s i o l o g y - 35: 36, 19ll+. 7. Bee r , E . L i g a t i o n o f the P o r t a l V e i n . Am. J . Med. S c . - 150: 5W, 3915. 8. Behrend, M . , Radasch, H . E . & Kerschner , A . G , Comparative R e s u l t s o f the L i g a t i o n o f the Hepa t i c A r t e r y i n A n i m a l s , A r c h . S u r g . - hi 661, 1922. 9 . Benz , E . J . , Baggenstoss , A . H . & Wol l aege r , E . E . The Pathogenesis o f At rophy o f the L . Lobe o f the L i v e r i n Man. Gas t roen te ro logy - 22: 3U, 1952. 10. Berman, J . K . & H u l l , J . E . E x p e r i m e n t a l A s c i t e s , i t s P r o d u c t i o n and C o n t r o l . Surgery - 32: 67, J u l y 1952. 11. B e r n a r d , C . L i q u i d e s de L ' o r g a n i s m e . P a r i s , J - B B a i l l i e r e e t F i l s . 2 : 1+65, 1859. 12. Be rna rd , C . Lecons su r l e d i abe te e t l a glycogenese a n i m a l e . P a r i s , J - B B a i l l i e r e e t F i l s , page 316, 1877. 13. B l a l o c k , A . & Mason, M . F . Observa t ions on the B l o o d Flow and Gaseous Metabol ism o f the L i v e r of Unanaes the t ized Dogs. Am. J . P h y s i o l . - 117: 328, 1936. lU. B l a l o c k , A . & Levy , S . The E f f e c t o f Haemorrhage, I n t e s t i n a l Trauma and His tamine on the P a r t i t i o n o f the B l o o d Stream. Am. J . P h y s i o l . - 118: 73U, 1937. 15. B o l l m a n , J . L . , S v i r b e l y , J . & Mann, F . C . B l o o d Concen t r a t i on I n f l u - enced by E ther and Amyta l A n a e s t h e s i a . Surgery - hi 881, 1938. Page 2 . 16. B o l o g n e s i , G . L i g a t u r e o f the P o r t a l V e i n i n Animals w i t h C i r c u l a - t i o n o f Jacobson: e x p e r i m e n t a l . A r c h , i t a l i e n n e de b i o l o g i e - U6: 5 1 , 1906-07. 17. B o l t o n , C . The P a t h o l o g i c a l Changes i n the L i v e r R e s u l t i n g from P a s s i v e Venous Conges t ion E x p e r i m e n t a l l y Produced. J . P a t h . & B a c t . - 19 : 258, 19LU. 1 8 . B o l t o n , C . & B a r n a r d , W.C. The P a t h o l o g i c a l Occurrences i n the L i v e r i n Expe r imen ta l Venous S t a g n a t i o n . J . P a t h . B a c t . - }h.t 701, 1931. 1 9 . B o n n y c a s t l e , D . D . & Cleghorn , R . A . A Study on the B l o o d Volume on a Group o f Un t r a ined Normal Dogs. Am. J . P h y s i o l . - 137; 380, 19U2. 20 . Boyce , F . F . , Lampert , R . & M c F e t r i d g e , E . M . O c c l u s i o n o f the P o r t a l V e i n . (An Expe r imen ta l Study w i t h i t s C l i n i c a l A p p l i - c a t i o n . ) J . L a b . & C l i n . Med. - 20 : 935, 1935. 2 1 . Boyce , F . F . & M c F e t r i d g e , E . M . A u t o l y s i s o f T issue i n V i v o . A r c h . S u r g . - 3U: 977, 1937. 2 2 . Boyce , F . F . The Role o f L i v e r i n Surge ry . C . C . Thomas, S p r i n g f i e l d , I l l i n o i s . Chap. 10, 1 9 l j l . 2 3 . Brewer , G . E . H y d a t i d C y s t o f L i v e r w i t h L i g a t u r e o f P o r t a l V e i n . A n n . S u r g . - i jT: 619, 1908. 2l+. Brewer , G . E . & G i e s , W . J . L i g a t i o n o f P o r t a l V e i n f o r Haemorrhage Dur ing Opera t ion on Hyda t id C y s t o f L i v e r . J . A . M . A . - 5 0 : 2 0 6 3 , 1908. 2 5 . Brunschwig , A . S u r g i c a l Treatment o f Carcinoma o f Body o f Pancreas . A n n . S u r g . - 120: 1*06, 191+1*. 26 . Brunschwig , A . , B i g e l o w , R . & N i c h o l s , S . E f f e c t i v e O c c l u s i o n and E x c i s i o n o f the P o r t a l V e i n . Surgery - 17: 781, 19145. 27 . B u r n e t t , W . E . , Rosemond, G . P . , Weston, J . K . & Tyson, R . R . S tud ies o f Hepat ic Response to Changes i n B l o o d Supp ly . S u r g i c a l Forum, American C o l l e g e o f Surgeons, 195l. 28 . B u r t o n - O p i t z , R. The V a s c u l a r i t y o f the L i v e r - I . The Flow o f B l o o d i n the Hepa t i c A r t e r y . Quar t . J . Exper . P h y s i o l o g y - 3 : 297, 1910. 29 . B u r t o n - O p i t z , R . The V a s c u l a r i t y o f the L i v e r - I I . The Inf luence o f the P o r t a l B l o o d Flow Upon the Flow i n the Hepa t ic A r t e r y . Quar t . J . E x p e r . P h y s i o l o g y - kt 93, 1911. Page 3 . 3 0 . B u r t o n - O p i t z , R . The V a s c u l a r i t y o f the L i v e r - I I I . The E f f e c t o f S t i m u l a t i o n of S i n g l e Nerves o f the Hepa t ic P lexus Upon the Flow i n the Hepat ic A r t e r y . Quar t . J. E x p . P h y s i o l . - kt 103, 1911. 31. B u r t o n - O p i t z , R . The V a s c u l a r i t y o f the L i v e r - I V . The Magnitude o f the P o r t a l I n f l o w . Quar t . J. Bcper. P h y s i o l . - 1+: 113, 1911. 3 2 . B u t l e r , H . The V e i n s o f the Oesophagus. Thorax - 6 : 2 7 6 , 1901. 3 3 . Cameron, G . R . & Mayes, B . T . L i g a t i o n o f Hepa t ic A r t e r y . J. P a t h . & B a c t . - 3J. : 799, 1 9 3 0 . 3h. C a n t l i e , J. On a NewArrangement o f the R i g h t and L e f t Lobes o f the L i v e r . P r o c . A n a t . Soc . G t . B r i t a i n & I r e l a n d - 3 2 : 1+, 1898. 3 5 . C a r r , D . T . & Essex , H . E . The Haemoglobin Concen t r a t i on o f the B l o o d o f I n t a c t and Splenectomized Dogs under P e n t o b a r b i t a l Sodium Anaes thes i a w i t h P a r t i c u l a r Reference t o the E f f e c t of Haemorrhage. Am. J. P h y s i o l . - ll+2: hO, 191+1+. 3 6 . C a s t a i g n e , J. & Bender, X . Sur l e s causes de mort apres l i g a t u r e brusque de l a ve ine p o r t e . A r c h . d e . Med. Expe r . - 111 751, 1 8 9 9 . 3 7 . Chand le r , L . R . Resis tance o f Hepa t ic T issues t o L o c a l Anaemia. P r o c . Soc . E x p e r . B i o l . & Med. - 1 8 : 2 3 , 1 9 2 0 - 2 1 . 3 8 . Charpy, A . Veine Po r t e i n P o i r i e r , P . and Charpy, A . " T r a i t e d ' anatomie humaine.'* 3 d . e d . b y A . N i c o l a s , P a r i s , Masson e t e i e , V o l . 2 , F a s c . 3 , A n g e i o l o g i e . 1920, pages 1 8 3 - 1 9 6 . 39. Chau, A . T . S . , Goldbloom, V . C . & Gurd , F . N . C l o s t r i d i a l I n f e c t i o n as a Cause o f Death a f t e r L i g a t i o n o f Hepat ic A r t e r y . A . M . A . A r c h . S u r g . - 6 3 : 3 9 0 , 1 9 5 l . 1*0. C h i l d , C . G . , McClu re , R . D . & Hays, D . M . S t u d i e s and the Hepa t ic C i r c u l a t i o n on the Macaca M u l a t t a Monkey and i n Man. S u r g . Forum, American C o l l e g e o f Surgeons, p g . ll+O, 1 9 f i l . 1+1. CjriJLd, C . G . , Holswade, G . R . , McLure , R . D . , Gore , A . L . & O ' N e i l l , E . A . Pancreaticoduodenectomy w i t h R e s e c t i o n o f the P o r t a l V e i n i n the Macaca M u l a t t a Monkey and i n Man. Su rg . , G y n . , Obs t . - %kt 31, 1 9 5 2 . 1+2. C h i l d , C . G . , B a r r , D . , Holswade, G .R . & H a r r i s o n , C . S . L i v e r Regener- a t i o n : P r e l i m i n a r y R e p o r t . P r o c . S o c . E x p e r . B i o l . & Med. - 8 2 : 2 8 3 , 1953. 1+3. C h i l d , C . G . , B a r r . D . , Holswade, G.8. & H a r r i s o n , C . S . L i v e r Regener- a t i o n F o l l o w i n g P o r t a c a v a l T r a n s p o s i t i o n i n Dogs. Ann. S u r g . - 138: 6 0 0 , 1 9 5 3 . Page 1+. 1+1+. C i b a Foundat ion Symposium on L i v e r D i s e a s e . The B l a k i s t o n C o . , P h i l a d e l p h i a 1951. 1+5. C o l p , R . The Treatment o f P y l e p h l e b i t i s o f Appendicu la r O r i g i n . S u r g . , G y n . , Obs t . - U3: 627, 1926. 1+6. Copher, G . H . St D i c k , B . M . "Stream L i n e " Phenomena i n the P o r t a l V e i n and the S e l e c t i v e D i s t r i b u t i o n o f P o r t a l B l o o d t o the L i v e r . A r c h . Surg . - 17 : 1+08, 1928. 1+7. C o u r t i c e , F . C . The B l o o d Volume o f Normal A n i m a l s . J . P h y s i o l . - 102: 290, 191+3. 1+8. C o u r t i c e , F . C . & Gunton, R.W. E f f e c t o f Nembutal Anaes thes i a on R e s t o r a t i o n o f Plasma Volume A f t e r Haemorrhage i n Dogs, Cats and R a b b i t s . J . P h y s i o l . - 1DQ: 1+18, 191+9. 1+9. C r o s s , F . S . , R a f f u c c i , F . L . , Toon, R.W. & Wangensteen, O . H . E f f e c t o f Complete Hepa t ic V e i n L i g a t i o n on P o r t a l Pressures and A s c i t e s Format ion i n Dogs w i t h P o r t a c a v a l Shunts . P r o c . S o c . E x p e r . B i o l . & Med. - 82 : 505, 1953. 50. D a v i s , L . , T a n t u r i , C . & T a r k i n g t o n , J . Reduced B l o o d Flow to the L i v e r i n R e n a l H y p e r t e n s i o n . S u r g . , G y n . , Obs t . - 89: 360, 191+9. 51. Delorme, E . J . A r t e r i a l P e r f u s i o n o f the L i v e r on Shock; and e x p e r i - mental S tudy . Lancet - 1: 259, 1951. 52. Delorme, E . J . , Macpherson, A . I . S . , Mukherjee, S . R . & Rowlands, S . Measurement o f V i s c e r a l B l o o d Volume i n Dogs. Quar t . J . E x p . P h y s i o l . - 36: 219, 1951. 53. Delorme, E . J . , Mukherjee, S . R . & Rowlands, S . S tud ie s o f the O i r c u - l a t i o n i n Haemorrhagic Shock by Means o f E r y t h r o c y t e s L a b e l l e d w i t h Radio Phosphorus. Qua r t . J . o f Expe r . P h y s i o l . - 37: 107, 1952. 5U. D i c k , B . M . "S t r eaml ines" on the P o r t a l V e i n - Inf luence i n S e l e c t i v e D i s t r i b u t i o n o f B l o o d i n the L i v e r . Edinburgh M . J . - 35: 533, Sep t . 1928. 55. Douglass , T . C . , Mehn, W . H . , Lounsbury, B . F . , Swige r t , L . L . & T a n t u r i , C . A . Attempts a t Exper imen ta l P r o d u c t i o n o f P o r t a l H y p e r t e n s i o n . A . M . A . A r c h . S u r g . - 62: 785, 195l. 56. Doyoh, St D u f o u r t . C o n t r i b u t i o n a l 1 e t u d e de l a f o n c t i o n u reopo ie t i que du f o i e . A r c h , de p h y s i o l . norm e t p a t h . - 10: 522, 1898. 57. Drags ted t , L . R . E f f e c t o f D i v e r s i o n o f B i l e i n t o Vena Cava & P o r t a l V e i n i n Dogs. P r o c . Soc . E x p e r . B i o l . & Med. - 26: 303, January 1929. Page 5 . 58. Drags t ed t , L . R . Gradua l 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 as a S u b s t i - t u t e f o r Eck F i s t u l a . Sc ience - 73: 315, 1931. 59. Dreyer , B . & B u d t z - O l s e n , O . E . S p l e n i c Venographyj demonstra t ion o f p o r t a l c i r c u l a t i o n w i t h d iodone . Lancet - 1: 530, 1952. 60 . Dvorak, H . J . l i v e r A u t o l y s i s i n the P e r i t o n e a l C a v i t y o f the Dog. P r o c . Soc . Expe r . B i o l . & Med. - 29 : I t f l , 1931-32. 6 1 . Eck , N . V . Kvoprosu o pe revyazk ie v o r o t n o i v e n i . Pudva r i t e l noye soobsh l s h i n z e . Voenno - m e d i t s i n s k i i Zhunual - 130: 2 S e c t . , 1, 1877. 62 . Edwards, E . A . F u n c t i o n a l Anatomy o f the Por tosys temic Communications. A r c h . I n t . Med. - 88: 137, 1951. 63. E l l i s , J . C . & Drags ted t , L . R . L i v e r A u t o l y s i s i n V i v o . A r c h . Su rg . - 20: 8, 1930. 6U. Elman, R . & C o l e , W . H . Loss o f B l o o d as a F a c t o r i n Death from Acute P o r t a l O b s t r u c t i o n . P r o c . Soc . Expe r . B i o l . & Med. - 29: 1122, 1932. 65. Elman, R . & C o l e , W.H. Cause o f Death i n Acute O b s t r u c t i o n o f P o r t a l V e i n . T r . Am. G a s t r o - e n t e r o l . A . - 36: 136, 1933. 66. Elman, R. & C o l e , W.H. Haemorrhage and Shock as Causes o f Death F o l l o w i n g Acute P o r t a l O b s t r u c t i o n . A r c h . S u r g . - 28: 1166, 193U. 67. E n g e l , F . L . , Win ton , M . G . & Long, C . N . H . The Metabol ism o f Amino A c i d s and Carbohydrate d u r i n g Haemorrhagic Shock i n the R a t . J . Expe r . Med. - 77: 397, 19k3, 68. E n g e l , F . L . , H a r r i s o n , H . C . & Long, C . N . H . The Role o f the L i v e r and the Hepat ic C i r c u l a t i o n i n the M e t a b o l i c Changes dur ing Haemorrhagic Shock i n Rat and C a t . J . Exp . Med. - 79: 9, 19hk. 69. Eze , W.C. Cause o f S u r v i v a l o f Dogs wi thou t Hepat ic A r t e r y . A . M . A . A r c h . S u r g . - 65,: 68U, 1952. 70. F i n e , J . Recent Advances i n Traumatic Shock. Advances i n Surgery - 1: 1, 19U9. 71. Foreman, R . C . R e d i s t r i b u t i o n o f R e s i d u a l B l o o d Volume i n Haemorrhagic Shock: r e l a t i o n t o l e t h a l b l e e d i n g volume. P r o c . Soc . Expe r . B i o l . & Med. - 65: 29, 19U7. 72. F rank , H . A . , Se l igman, A . M . & F i n e , J . Traumatic Shock - X I I The p r e - v e n t i o n o f i r r e v e r s i b i l i t y i n Haemorrhagic Shock by v i v i p e r f u s i o n o f the l i v e r . J . C l i n . I n v e s t . - 25: 22, 19U6. Page 6. 73. F rank , H . A . , Jacob, S .W. , Schweinburg, F . B . , Goddard, J . & F i n e , J . Traumatic Shock - XXI E f f e c t i v e n e s s o f an A n t i b i o t i c i n Expe r imen ta l Haemorrhagic Shock* Am. J . P h y s i o l . - 168: 1*30, 1952. 7k. F r a s e r , D . , Rappaport , A . M . , V u y l s t e k e , C . A . & C o l w e l l , A . R . E f f e c t s o f L i g a t i o n o f the Hepa t i c A r t e r y i n Dogs. Surgery - 3 0 : 621*, 1951. 7 5 . F r e r i c h s , F . T . Pa tho log i sch-ana tomischer A t l a s zur K l i n i k der L e b e r k r a n k h e i t e n . Braunschweig, F . Vieweg u . Sohn, l 8 5 l . 76. G i b s o n , J . G . , Se l igman, A . M . Peacock, W . C . , Aub, J . C . & F i n e , J . The D i s t r i b u t i o n o f Red C e l l s and Plasma i n Large and Minute V e s s e l s o f the Normal Dog, Determined by R a d i o - a c t i v e Isotopes o f I r o n and I o d i n e . C l i n . I n v e s t . - 2 5 : 81*8, 19U6. 77. G i l d i n g , H . P . S tud i e s o f T i s sue Maintenance; S e r v i c e t o IAver and D i g e s t i v e T r a c t a f t e r Haemorrhage. J . E x p e r . Med. - 5 0 : 213, 1 9 2 9 . 78. G i n t r a c . Schmor l . J a h r b . - 9 3 : 1857. 79. G l e n a r d , F . Des r e s u l t a t s o b j e c t i f s de l ' e x p o r a t i o n du f o i e chez l e s d i a b e t i q u e s . Lyon Med. - i j * : pages - 5 , 80, 115, 189, 2 5 9 , - 1890. 80. Goldschmidt , S . , . R a v d i n , I . S . & Lucke , B . The P r o t e c t i v e A c t i o n o f Oxygen A g a i n s t the N e c r o t i z i n g E f f e c t o f C e r t a i n A n a e s t h e t i c s on the L i v e r . J . Pharmacol . - 5 9 : 1, 1937. 81. Graham, R . R . & C a n n e l l , D , A c c i d e n t a l L i g a t i o n o f the Hepa t ic A r t e r y . B r i t . J . S u r g . - 2 0 : 5 6 6 , 1 9 3 2 - 3 3 . 82. Gran t , J . L . , F i t t s , W . T . , R a v d i n , I . S . Aneurysm o f the Hepat ic A r t e r y . S u r g . , G y n . , Obs t . - £ 1 : 5 2 7 , 1 9 5 0 . 83. Gregersen, M . I . & Rawsoh> R . A . The Disappearance o f T-1821* and S t r u c t u r a b l y R e l a t e d Dyes from the B l o o d St ream. Am. J . P h y s i o l . - 138: 6 9 8 , 191+2-1*3. 81*. Gregersen, M . I . , Boyden, A . A . & A l l i s o n , J . B . D i r e c t Comparison i n Dogs o f Plasma Volume Measured w i t h T-1821* and w i t h A n t i g e n s . Am. J . P h y s i o l . - 163: 517, 1 9 5 0 . 8 5 . G r i n d l a y , J . H . , H e r r i c k , J . F . & Mann, F . C . Measurement o f the B lood Flow Through the L i v e r . Am. J . P h y s i o l . - 132: 1*89, March 19l*l. 86. G r i n d l a y , J . H . , Mann, F . C . & B o i l m a n , J . L . E f f e c t o f Occ lus ion , o f the A r t e r i a l B l o o d Supply o f the Normal L i v e r . A r c h . S u r g . - 6 2 : 8 0 6 , 1 9 5 l . Page 7. 87. G r i n d l a y , J . H . & B o l l m a n , J . L . Regenera t ion o f L i v e r i n Dog a f t e r P a r t i a l Hepatectomy - Ro le o f Venous C i r c u l a t i o n . S u r g . , G y n . , Obs t . - 9l{.: 1+91, 1902. 88. Haberer . E x p e r i m e n t e l l e unterbindung der A r t e r i a h e p a t i c a . V e r h a n d l . d . deu t sch . G e s e l l s c h . f . C h i r . - 3J+: 167, 1905. 89. Hahn, P . F . , Ross , J . F . , B o l e , W . F . , B a l f o u r , W.M. & Whipp le , G . H . Red C e l l and Plasma Volumes ( c i r c u l a t i n g & t o t a l ) as Determined by Radio I ro n and b y Dye. J . E x p e r . Med. - 75: 221, 191+2. 90. Hahn, P . F . , B a l e , W . F . & Bonner, J . F . Removal o f Red C e l l s from the A c t i v e C i r c u l a t i o n by Sodium P e n t o b a r b i t a l . Am. J . P h y s i o l . - 138: 1+15", 191+2-1+3. 9 1 . Hahn, P . F . , Dona ld , W.D. & G r i e r , R . C . J r . The P h y s i o l o g i c a l B i l a t e r a l i t y o f the f b r t a l C i r c u l a t i o n Stream L i n e Flow o f B l o o d i n t o the L i v e r as Shown by R a d i o - a c t i v e Phosphorus. Am. J . P h y s i o l . - 32+3s 105", 191+5. 92. H a l l e t , E . B . , H o l t o n , G.W. , Pa t e r son , J . C . S . & S c h i l l i n g , J . A . L i v e r B l o o d F low, Hepa t ic Glucose P r o d u c t i o n and Sp lanchn ic Oxygen Consumption i n Normal Dogs and F o l l o w i n g Eck F i s t u l a : l i v e r b l o o d f l ow before and a f t e r splenectomy. S u r g . , G y n . , Obs t . - 95:1+01, 1952. 93. Hardy, E . G . , M o r r i s , G . C . , Yow, E . M . , Haynes, B . W . , & DeBakey, M . E . S tud ie s i n the Ro le o f B a c t e r i a i n I r r e v e r s i b l e Haemorrhagic Shock i n Dogs. Ann . S u r g . - 139: 282, 1951+. 9l+. Hausner, E . , Essex , H . E . & M a n n , F . C . Roentgenologic Observa t ions o f the Spleen o f the Dog under E t h e r , Sodium A m y t a l , P e n t o b a r b i t a l Sodium and P e n t o t h a l Sodium A n a e s t h e s i a . Am. J . P h y s i o l . - 321 : 387, 1938. 95. Hay, E . B . & Webb, J . K . E f f e c t o f Increased A r t e r i a l B l o o d Flow t o L i v e r on M o r t a l i t y Rate F o l l o w i n g Haemorrhagic Shock. Surgery - 29: 826, 1 9 5 l . 96. Hevesy, G . & Zerahn, K . De te rmina t ion o f Red Corpusc le Conten t . A c t a P h y s i o l . Scand. - hi 376, 191+2. 97. Hoffbauer , F . W . , B o l l m a n , J . L . & G r i n d l a y , J . H . F a c t o r s I n f l u e n c i n g Pressure i n the P o r t a l V e i n as Measured i n the I n t a c t A n i m a l . J . L a b . & C l i n . Med. - 32: l l+Ol, 19U7. 98. Holmes, R . O . & L o v i t t , W.V. S t u d i e s o f the P o r t a l Venous System b y I n j e c t i o n Technique. Gas t roen te ro logy - 1J_: 209 1951. 99. Huggins , C . & P o s t , J . Expe r imen ta l S u b t o t a l L i g a t i o n o f the A r t e r i e s Supply ing the L i v e r . Arch .Surg . -35:878, 1937. Page 8. 1 0 0 . Huizenga , K . A . , Brofman, B . L . • & Wiggers , C . J . The I n e f f e c t i v e n e s s o f A d r e n a l Cor tex E x t r a c t s i n S tandard ized Haemorrhagic Shock. J . Pharmacol . & Expe r . Therap. - 7 8 : 139, 1 9 a 3 . 1 0 1 . Ingraham, R . C , Goldberg , H . , Roemhi ld , F . & Wiggers , H . C . In f luence o f Sodium P e n t o b a r b i t a l upon Course o f Events i n E x p e r i - menta l Haemorrhagic Shock. Am. J . P h y s i o l . - l6_2: 2l*3, 1950, 102. I r eneus , C . & Puestow, C . B . E f f e c t o f Mass ive Expe r imen ta l Haemorrhage i n Hepat ic F u n c t i o n on Dogs. A r c h . Su rg . - 1*9: 100,191*1*. 1 0 3 . I t o , H . & O r a l , K . K l i n i s c h e und e x p e r i m e n t e l l e Beitr 'age zu r c h i r u r - g i schen Behandlung des A s c i t e s . Deutsche Z t s c h r . F . C h i r . - 6 2 : l l + l , 1 9 0 1 - 0 2 . 101*. Jackson , H . C . The E f f e c t o f C o n d i t i o n s Upon the La ten t P e r i o d and Rate o f A s e p t i c P o s t Mortem A u t o l y s i s Dur ing the F i r s t Ten Hours . J . Expe r . Med. - 11$ 5 5 , 1909. 1 0 5 . Jaques, L . B . , F i d l a r , F e l d s t e d , E . T . & Macdonald, A . G . S i l i c o n e s and B l o o d C o a g u l a t i o n . Can . Med. A s s o c . J . - 5 5 : 2 6 , 191*6. "~ 1 0 6 . J a r c h o , L . W . The E f f e c t o f Nembutal and Ether Anaes thes i a Upon B l o o d C o n c e n t r a t i o n . Am. J . P h y s i o l . - 138: 1*58, 19l*2. 1 0 7 . J e f f e r s o n , N . C . , P r o f f i t t , M . M . & Neche les , H . C o l l a t e r a l C i r c u l a t i o n t o the L i v e r o f the Dog. Surgery - 3 1 : 721*, 1952. 1 0 8 . Johnson, G . S . & B l a l o c k , A . Expe r imen ta l Shock. LY. - A Study o f the E f f e c t s o f the Loss o f Whole B l o o d , or B l o o d Plasma and o f Red B l o o d C e l l s . A r c h . S u r g . - 2 2 : 626, 1931. 1 0 9 . K a t z , L . N . & Rodbard, S . The I n t e g r a t i o n o f the Vasomotor Responses i n the L i v e r w i t h Those i n Other Systemic V e s s e l s . J . Pharmacol . & Expe r . Therapeut ics - 6 7 : 1*07, 1 9 3 9 . 110. K i r s h n e r , D . , Hooton, T . C . & Shearer , E . M . P r o d u c t i o n o f Exper imen ta l P o r t a l Hyper tens ion i n Dog. Anatomy o f Hepat ic Ve ins i n Dogs. A r c h . S u r g . - 5 3 : 1*25, 19l*5. 111. K r i e g e r , H . , S t o r a a s l i , J . P . , F r i e d e l l , H . L . & Holden , W.D. A comparat ive Study o f B l o o d Volume i n Dogs. P r o c . Soc . Expe r . B i o l . Med. - 6 8 : 511, 19l*8. 112. K u n k e l , H . G . & Eisenmenger, W . J . Increased P o r t a l Pressure and A s c i t e s i n Rats 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 . P r o c . Soc . Expe r . B i o l . & Med. - 71 : 212, 19i*9. 113 . K u n t z , A . & Haselwood, L . A . C u t a n e o - v i s c e r a l Vasomotor Ref l exes i n the C a t . P r o c . Soc . Expe r . B i o l . Med. - 1*3: 517,19l*0. Page 9. 13l+. Laufman, H . , C r a i g , R . L . & P u r r , W.E . J r . R e c i p r o c a l H y d r o s t a t i c R e l a t i o n s h i p Between P o r t a l and C a v a l Systems: i t s a p p l i c a t i o n t o problem o f a s c i t e s . S u r g i c a l Forum, C l i n i c a l Congress o f Am. . C o l l . S u r g . , W.B . Saunders - p g . 158, 1951. 115. Laufman, H . , F u r r , W . E . , Ross , A . , C r a i g , R . L . & Bernhard , V . P a r t i a l O c c l u s i o n o f the P o r t a l V e i n i n Expe r imen ta l A s c i t e s . A . M . A . A r c h . Surgery - 6 5 : 886, 1952. 116. Lauteribach, B . F . On a New F u n c t i o n o f the L i v e r . M e d i c a l Times Sc R e g i s t e r - 7: 387, 1876-77. 117. Lawson, H . The Measurement o f B l e e d i n g Volume i n the Dog f o r S tud ie s on B l o o d S u b s t i t u t e s . Am. J . P h y s i o l . - U+0: 1+20, 191+3. 118. L e w i s , F . J . & Wangensteen, O . H . P e n i c i l l i n i n Treatment o f P e r i - t o n i t i s Due to L i v e r A u t o l y s i s i n Dogs. P r o c . Soc . E x p e r . B i o l . & Med. - 73: 533, 1950. 119. L o e f f l e r , L . F a c t o r s Determining N e c r o s i s o r S u r v i v a l o f L i v e r T i s sue a f t e r L i g a t i o n o f Hepat ic A r t e r y . A r c h . P a t h . - 21: 1+96, 1936. 120. Lund, H . , S tewar t , H . L . & L i e b e r , M . M . Hepat ic I n f a r c t i o n . Amer. J . P a t h . - 11: 157, 1935. 121. Mclndoe , A . H . & C o u n s e l l o r , V . S . The B i l a t e r a l i t y o f the L i v e r . A r c h . S u r g . - 35: 589, 1927. 122. Mclndoe, A . H . V a s c u l a r L e s i o n s o f P o r t a l C i r r h o s i s . A r c h . P a t h . - 5: 23, 1928. 123. M c l v e r , M . A . & W i n t e r , E . A . D e l e t e r i o u s E f f e c t s o f Anox ia on the L i v e r o f the Hyper t h y r o i d A n i m a l . A r c h . S u r g . - 1*6: 171, 191+3. 121+. M c L a i n , P . L . , Ruhe, C .H.W. & Kruse , T . K . Concurrent Es t imates o f B l o o d Volume i n Animals by B l e e d i n g and Dye Methods. Am. J . P h y s i o l . - l 6 U : 6 l l , 195 l . 125. M c M i c h a e l , J . The P o r t a l C i r c u l a t i o n - 1. The A c t i o n o f A d r e n a l i n e and P i t u i t a r y Pressor . E x t r a c t . J . P h y s i o l . - 75: 2l+l, 1932. 126. McMichae l , J . The P o r t a l C i r c u l a t i o n - 2. The A c t i o n o f A c e t y l - c h o l i n e . J . P h y s i o l . - 77: 399, 1933. 127. McMichae l , J . & Smirk , F . H . E f f e c t o f Exper imen ta l P o r t a l Conges t ion on A b s o r p t i o n and E x c r e t i o n o f Water . J . P a t h . & B a c t . - 37: 81, 1933. Page 10. 128. McMichae l , J . The Oxygen Supply o f the L i v e r . Quar t . J . Exper . P h y s i o l o g y - 27 : 73, 1937. 129. M a l l , F . P . The C o n t r a c t i o n o f the Vena Por tae and i t s In f luence Upon the C i r c u l a t i o n . Johns Hopkins Hosp. Rep. - 1: 111, 1896. 130. M a l l e t - g u y , P . , D e v i c , G . & Gangolphe, M. Sudden Expe r imen ta l I n t e r r u p t i o n o f P o r t a l V e i n . Lyon C h i r u r g i c a l - 16 i 929, 1950. 131 . Mann, F . C . & Magaths, T . B . The P r o d u c t i o n o f Chronic L i v e r I n - s u f f i c i e n c y . Am. J . P h y s i o l . - 59: 1+85, 1922. 132. Mann, F . C . P e r s o n a l Communications t o Mason, 1925, and to Markowi tz , 191+9. 133. Mann, F . C , F i s h b a c k , F . C , Gay, J . G . & Green, G . F . Expe r imen ta l Pa tho logy o f the L i v e r - I I I , IV & V . A r c h . P a t h . - 12: 787, 1931. 13l+. Mann, F . C . The P o r t a l C i r c u l a t i o n and R e s t o r a t i o n o f the L i v e r a f t e r P a r t i a l Removal. Surgery - 8: 225, 191+0. 135. Mann, F . C . The C i r c u l a t i o n o f the L i v e r . Quar t . B u l l . Ind iana U n i v . Med. Centre - hi 1+3, 191+2. 136. Mann, F . C . The G a s t r o - i n t e s t i n a l T r a c t and L i v e r . J . A . M . A . - 121: 720, 191+3. 137» Markowi t z , C . and Mann, F . C S tud ie s on P h y s i o l o g y o f L i v e r ; Role o f L i v e r i n Format ion o f Lymph, Am. J . P h y s i o l . - 96: 709, 1931. 138, Markowi t z , J . Expe r imen ta l S u r g e r y . W i l l i a m s & W i l k i n s C o . , B a l t i m o r e , 191+9. 139 . Markowi tz , J . , Rappaport , A . & S c o t t , A . C P r e v e n t i o n o f L i v e r N e c r o s i s F o l l o w i n g L i g a t i o n o f Hepat ic A r t e r y . P r o c . Soc . Expe r . B i o l . & Med. - 70: 305, 191+9. ll+O. Markowi t z , J . & Rappaport , A . The Hepat ic A r t e r y . P h y s i o l . Rev. - 3 1 : 188, 1951. l l + l . M a r t i n , G . H . , B u n t i n g , C . H . St Loevenhar t , A . S . The M o r p h o l o g i c a l Changes i n the T i s sues of the Rabb i t as a R e s u l t o f Reduced O x i d a t i o n s . J . Pharmacol . - 8: 112, 19l6. 11+2. Mason, E . C & Davidson , E . C T i s s u e A u t o l y s i s i n V i v o - I . B l o o d Changes, P h y s i c a l and C h e m i c a l . J . L a b . & C l i n . M e d . - 10: 622, 1921+-25. Page 11. l l+3. Mason, E . G . & Davidson , E . C . I I . Pha rmaco log ica l Study o f Tox ic M a t e r i a l . J . L a b . & C l i n . Med. - 10 : 9 0 6 , 192l*-25. 114;. Mason, E . C . & Davidson , E . C . I I I . Observa t ions .Using the S p l e e n . J . L a b . & C l i n . Med. - 10: 9 9 7 , 1921-25. 11*5. Mason, E . C . & Har t , M . S . The W e l c h - l i k e B a c i l l u s i n the Human L i v e r . J . L a b . & C l i n . Med. - 2 5 : 8 3 5 , 191*0. l l+6, M i c h e l s , N . A . C o l l a t e r a l A r t e r i a l Pathways to the L i v e r a f t e r L i g a t i o n o f the Hepat ic A r t e r y and Removal o f C o e l i a c A x i s . Cancer - 6 : 7 0 8 , 1953. 11+7. M i l n e s , R . F . & C h i l d , C . G . Acute O c c l u s i o n by L i g a t i o n o f the P o r t a l V e i n i n Macacus Rhesus Monkey. P r o c . Soc . E x p e r . B i o l . & Med. - 7 0 : 3 3 2 , 191+9. 11*8. M i l n e s , R . F . Hepat ic A r t e r y L i g a t i o n i n Rabb i t s Fo l lowed by Thorac ic C a v a l C o n s t r i c t i o n . P r o c . S o c . E x p . B i o l . & Med. - 77: 653, .1951. li+9. M i l n e s , R . F . An E v a l u a t i o n of Hepa t i c & S p l e n i c A r t e r y L i g a t i o n i n Dogs w i t h Expe r imen ta l A s c i t e s . Surgery - 3 2 : 701+, 1952. 1 5 0 . M o r r i s , A . N . & M i l l e r , H . H . Chronic P o r t a l V e i n O c c l u s i o n & P o r t a l Hyper tens ion i n the Dog. Surgery - 3 0 : 768, 1951. 1 5 1 . MosseLnan & L i e n a u x . Sur l a cause de l a mort^apres l a l i g a t u r e de l a v e i n e p o r t e . Ann de Med. v e t e r i n a i r e - 3l+: 1+67, CU~^. 1 8 8 5 . " — 152. Myers , J . D . & Hickham, J . B . E s t i m a t i o n o f Hepa t ic B l o o d Flow and Op Consumption i n Heart F a i l u r e . J . C l i n . I n v e s t . - 2 7 : 6 2 0 , Sep t . 19U8. 153. Myers , J . D . & T a y l o r , W . J . The E s t i m a t i o n o f P o r t a l Venous Pressures by O c c l u s i v e C a t h e t e r i z a t i o n o f an Hepat ic Venu le . J . C l i n . I n v e s t . - 3 0 : 6 6 2 , 195l. 151+. N a e g e l i , T . & Der ra , E . E f f e c t o f L i g a t i o n o f P o r t a l & S p l e n i c Ve ins on B l o o d Gases & B l o o d Volume. Schweiz . Med. Wchnschr . - 65: 8 6 , 1935. 155. N e l s o n , R . M . M e t a b o l i c E f f e c t s o f Pa raco lon Bac t e r emia . Ann . S u r g . - 131+: 8 8 5 , 1951. 156. N e l s o n , R . M . & Noyes, H . E . B l o o d C u l t u r e S tud ies i n Normal Dogs and i n Dogs w i t h Haemorrhagic Shock. Surgery - 3 5 : 782, 1951*. / ** 157. N e t t e r . A r c h . Gen. de Med. - 1881*. Page 12 . 158. Neuhof, H . Expe r imen ta l L i g a t i o n o f the P o r t a l V e i n : i t s a p p l i c a t i o n t o the t reatment o f suppura t ive p y l e p h l e b i t i s . S u r g . , G y n . , Obs t . - 16: i+8l, 1913. 109. N y l i n , G . & Mahn, M . C o n c e n t r a t i o n o f Red B l o o d Corpusc les Con- t a i n i n g L a b e l l e d Phosphorus Compounds i n the A r t e r i a l B l o o d a f t e r the Intravenous I n j e c t i o n . Am. J . Med. S c . - 2 0 7 : 7 U 3 , 19W+. 1 6 0 . N y l i n , G . C i r c u l a t o r y B l o o d Volume o f Some Organs. Am. Heart J . - 3j±: 17U, 191+7. 161. Ore . In f luence de 1 ' o b l i t e r a t i o n de l a ve ine po r t e sur l a s e c r e t i o n de l a b i l e e t sur l a f o n c t i o n g lycogenique du f o i e . Compte rendu A c a d . R o y a l d . S c . - 1+3: 1+63, 1856. 1 6 2 . Pa ton , A . , Reynolds , T . B . & S h e r l o c k , S . Assessment o f P o r t a l Venous Hyper tens ion by C a t h e t e r i z a t i o n o f Hepat ic V e i n . Lance t - 2 6 U : 918, 1 9 5 3 . 1 6 3 . Peck, M . E . & Grover , R . F . C a r d i o v a s c u l a r Responses t o Acute L i g a t i o n o f P o r t a l V e i n . A . M . A . A r c h . S u r g . - §ht 6 6 5 , 1952. l61+. P i c k , L . Ueber t o t a l e hamangiomatose O b l i t e r a t i o n des Pfortaderstammes und fiber hepatopeta le K o l l a t e r a l b a h n e n . V i r c h o w ' s A r c h , f . p a t h . A n a t . B e r l . - 197: 1+90, 1 9 0 9 . 1 6 5 . Popper, H . L . , J e f f e r s o n , N . C . & Neche les , H . I n t e r r u p t i o n o f A l l A r t e r i a l B l o o d Supply t o L i v e r not Compatible w i t h L i f e . Am. J . Surgery - 8lj.: 1+29, 1952. 166. Popper, H . L . , J e f f e r s o n , N . C . & Necheles , H . L i v e r N e c r o s i s F o l l o w i n g Complete I n t e r r u p t i o n o f Hepat ic A r t e r y and P a r t i a l L i g a t i o n o f P o r t a l V e i n . Am. J . Surgery - 8 6 : 3 0 9 , 1953. 1 6 7 . R a f f u c i , F . L . & Wangensteen, O . H . Tolerance o f Dogs t o O c c l u s i o n o f E n t i r e A f f e r e n t V a s c u l a r Inf low to L i v e r . " S u r g i c a l Forum" American C o l l e g e o f Surgeons . W . B . Saunders C o . , P h i l a d e l p h i a , 1 9 5 l . Pages 1-5, 1951. 1 6 8 . R a f f u c i , F . L . The E f f e c t s o f Temporary O c c l u s i o n o f the A f f e r e n t Hepat ic C i r c u l a t i o n i n Dogs. Surgery - 33: 31+2, 1953. 169. Rappaport , A . M . Expe r imen ta l Ischaemia o f L i v e r and Hepat ic Coma. " L i v e r I n j u r y " Conference J o s i a h Macy J r . Found - page lU6, 1951. 170. Rappaport , A . M . , C l a r k e , D.W. & S tewar t , M . E f f e c t o f L i v e r Ischaemia on Plasma i n Dogs, as Measured by ELec t rophores i c A n a l y s i s . P r o c . S o c . Expe r . B i o l . & Med. - 8 0 : 5 8 5 , 1952. 171 . Reeve, E . B . & V e a l l , N . A S i m p l i f i e d Method f o r the De te rmina t ion o f C i r c u l a t i n g Red C e l l Volume w i t h R a d i o a c t i v e Phosphorus. J . P h y s i o l . - 108: 12 , 191+9. Page 13 . 172 . Robe r t s , G . M . & C r a n d a l l , L . A . J r . Role o f P o r t a l System i n Regu- l a t i o n o f C i r c u l a t i n g B l o o d Volume. Am. J . P h y s i o l . - 106: 1+23, 1 9 3 3 . 173 . Robe r t s , L . N . , S m i l e y , J . R . , Sea r s , G . A . & Manning, G.W. Plasma Volume Measured by I o d i n a t e d Albumin and T.1821+. Canad. M . A . J . - 6 9 : 510, 1953. 17l+. R o l l e s t o n , H . & McNee, J . W . Diseases o f the L i v e r , G a l l B ladder and B i l e D u c t s . 3 r d E d . London, M a c M i l l a n & C o . L t d . Page 2 2 , 1 9 2 9 . 175. Romieu, C . & Brunschwig , A . A B a c t e r i o l o g i c Study o f the Human L i v e r . Surgery - 3 0 : 621, 1901. 176. Roorae, N . W . , K e i t h , W . S . & Phemis te r , D . B . Expe r imen ta l Shock, The E f f e c t o f B l e e d i n g A f t e r Reduc t ion o f B l o o d Pressure By Var ious Methods. S u r g . , G y n . , Obs t . - 5 6 : l 6 l , 1 9 3 3 . 177 . Rous, P . & L a r r i m o r e , L . D . R e l a t i o n o f P o r t a l B l o o d t o L i v e r Main tenance . J . E x p e r . Med. - 3 1 : 609, 1920. 178 . Rous, P . , G i l d i n g , H . P . & Smi th , M . B . The Grad ien t o f V a s c u l a r P e r m e a b i l i t y . J . Exp . Med. - 5 l : 807, 1 9 3 0 . 179. S a l z b e r g , A . M . & Evans, E . I . B l o o d Volumes i n Normal and Burned Dogs. A n n . S u r g . - 132: 7U6, 1 9 5 0 . 180. Sance t t a , S . M . Dynamic & Neurogenic F a c t o r s Determining the Hepat ic A r t e r i a l Flow a f t e r P o r t a l O c c l u s i o n . C i r c . Res . - 1: hlh, 1 9 5 3 . 181 . Sappey, C . Memoire sur l e s ve ines po r t e s a c c e s s o i r e s . J . A n a t . e t P h y s i o l . - 19 : 517, 1883. 182 . Sborov, V . M . , Morse , W . C . , G i g e s , B . & Jahnke, E . J . B a c t e r i o l o g y o f the Human L i v e r . J . C l i n . I n v e s t . - 3 1 : 9 8 6 , 1952. 183. Schafe r , P .W. & Kozy, J . S . R a d i c a l Pancreatoduodenectomy w i t h R e s e c t i o n o f Pa ten t P o r t a l V e i n : expe r imen ta l s t udy . Surgery - 2 2 : 9 5 9 , 19U7. 181+. S c h i f f , M . C e n t r a l b l . f . d . Med. Wissensch . - 8: 115, I863. 1 8 5 . S c h i l l i n g , H . , McKee, F .W. & W i l k , W. Expe r imen ta l Hepat ic P o r t a l A r t e r i o venous Anas tomosis . S u r g . , G y n . , Obst . - £ 0 : 1+73, 1 9 5 0 . 186 . Schraiedel , G . C . De v a r i e t a t i o n s vasorum magni pleurumque momenti, 17UU. Page 14. 187. Schocken, K . The P h y s i c a l P r i n c i p l e s o f B l o o d C i r c u l a t i o n . E x p . Med. S u r g . - 2 : 73 , 1953. 188. Schwiegk, H . Untersuchungen tfber d i e Leberdurchblutung und den P f o r t a d e r k r e i s l a u f . A r c h . F . exper . P a t h . u . Pharmakol . - 168: 693, 1932. 189. Seave r s , R . & P r i c e , P . B . E f f e c t s and Fa te o f B l o o d Trans fus ions i n Normal Dogs. A r c h . S u r g . - 59: 275, 1949. 190. S e g a l l , H . N . E x p e r i m e n t a l A n a t o m i c a l I n v e s t i g a t i o n o f B l o o d and B i l e Channels of the L i v e r ; compensatory a r t e r i a l c i r c u l a t i o n o f the l i v e r i n i t s r e l a t i o n t o s u r g i c a l l i g a t i o n o f h e p a t i c a r t e r y ; r e p o r t o f a case o f a r t e r i o s c l e r o t i c aneurysm o f gas t roduodenal a r t e r y . S u r g . , G y n . , Obs t . - 37 : 152, 1923. 1 9 1 . S e l k u r t , E . E . , A lexande r , R . S . & P a t t e r s o n , M . B . The Ro le o f the Mesen te r i c C i r c u l a t i o n i n the I r r e v e r s i b i l i t y o f Haemorrhagic Shock. Am. J . P h y s i o l . - 149: 732, 1947. 192. S e n e v i r a t n e , R . D . P h y s i o l o g i c a l and P a t h o l o g i c a l Responses i n the B l o o d V e s s e l s o f the L i v e r . Quar t . J . E x p e r . P h y s i o l . - 35 : 77 , 1950. 193 . Serege . C o n t r i b u t i o n a 1*etude de l a c i r c u l a t i o n du faug por te dans l e f o i e a t des l o c a l i s a t i o n s l o b a i r e s hepa t iques . J . de Med. de Bordeaux - 3 1 : 371, 291, 312, 1901. 194. S h o r r , E . , Zwe i fach , B . W . , F u r c h g o t t , R . F . & Baez , S . Hepa to - rena l F a c t o r s i n C i r c u l a t o r y Homeostas is . C i r c u l a t i o n - 3 : 42 , 1951. 195 . Simonds, J . P . & A r e y , L . B . The R e l a t i o n o f the Smooth Muscle i n the Hepa t i c Ve ins t o Shock Phenomena. A n a t . R e c . - 18; 219, 1920. 196. Simonds, J . P . & Brandes , W.W. The E f f e c t o f O b s t r u c t i o n o f the Hepa t i c Ve ins i n the Sys temic C i r c u l a t i o n . Am. J . P h y s i o l . - 7 2 : 320, 1925. 197. Simonds, J . P . & Brandes , W.W. I A n a p h y l a c t i c Shock and Mechan ica l O b s t r u c t i o n o f the Hepa t ic Ve ins i n the Dog. I I The E f f e c t o f Mechan i ca l O b s t r u c t i o n o f the Hepa t i c Ve ins upon the Outf low o f Lymph from the T h o r a c i c D u c t . J . Immunol. - 1 3 : 1, 1927. 198. Simonds, J . P . & Brandes , W.W. The E f f e c t of Peptone Upon the Hepa t i c Ve ins i n the Dog. J . pharm. & E x p e r . Therap. - 35 : 165, 1929. Page 15. 199. Simonds, J . P . & C a l l o w a y , J .W. Ana tomica l Changes i n the l i v e r s o f Dogs F o l l o w i n g M e c h a n i c a l C o n s t r i c t i o n o f the Hepa t ic V e i n s . Amer. J . P a t h . - 8: 359, 1932. 200. Simonds, J . P . & Je rgesen , F . H . La te Changes i n the L i v e r Induced By M e c h a n i c a l O b s t r u c t i o n o f the Hepa t i c V e i n s . A r c h . P a t h . - 20: 5 7 1 , 1935. 2 0 1 . Smi th , H . P . , A r n o l d , H . R . & Whipp le , G . H . B l o o d Volume S t u d i e s : V I I Comparative Va lues o f Welcker Carbon Monoxide De t e r - mina t ions j accura te e s t i m a t i o n o f abso lu te b l o o d volume. Am. J . P h y s i o l . - 56: 336, 1921. 202. Smythe, C M . , F i t z p a t r i c k , H . F . & Blakemore, A . H . S tud ies o f P o r t a l Venous Oxygen Content i n Unaes the t i zed Man. J . C l i n . I n v e s t . - 3 0 : 67l+, 1 9 5 l . 203. S o l o w i e f f . A r c h . P a t h . A n a t . - 62: 195, 1875. 20l+. S t o p f o r d , J . S . B . The P o r t a l Systemic Anastomoses. M e d i c a l C h r o n i c l e - 6 1 : 12, 1915. 2 0 5 . T a n t u r i , C , S w i g a r t , L . L . & Canepa, J . F . ^P reven t ion o f Death from Exper imen ta l L i g a t i o n o f the Idver (hepa t ic proper) Branches o f the Hepa t ic A r t e r y . S u r g . , G y n . , Obs t . - 91: 680, 1 9 5 0 . 206. Tappeiner , H . Ueber den Zustand des B lu t s t romes nach Unterbindung der P f o r t a d e r . A r b e i t , a . d . p h y s i o l . A n s t . z . L e i p z i g . 1873. 207. Thomas, W . D . , & Essex , H . E . Observat ions on the Hepat ic Venous C i r c u l a t i o n w i t h S p e c i a l Reference t o the S p h i n c t e r i c Mechanism. Am. J . P h y s i o l . - 358* 303, 191+9. 208. T o n o l l i , G . O b e r t i . Expe r imen ta l Sudden and T o t a l L i g a t i o n o f P o r t a l V e i n i n R e l a t i o n to Genesis o f A s c i t e s . B o l l . S o c . I t a l , b i o l . s p e r . - 23: 1233, 191+7. 209. T r u s l e r , H . M . & Reeves, J . R . S i g n i f i c a n c e o f Anaerobic Organisms i n P e r i t o n i t i s due to L i v e r A u t o l y s i s . A r c h . Surg . - 28: 1+79, 1931+., 2 1 0 . T r u s l e r , H . M . & Reeves, J . R . & M a r t i n , H . E . S i g n i f i c a n c e o f Anaerobic Organisms i n P e r i t o n i t i s Due to L i v e r A u t o l y s i s . A r c h . S u r g . - 30: 371, 1 9 3 5 . 211. T r u s l e r , H . M . & M a r t i n , H . E . The Cause o f Death i n L i v e r P e r i t o n i t i s . Surgery - 1: 2l+3, 1937. 212. T s c h e r n i k o f f , A . M . , Malenjuk, W.W., J a k u b o v i t s c h , M . E . & K l a n t a r o f f , M . C h . A r c h . f . d . P h y s i o l . - 227: 8 5 , 1 9 3 1 . Page 1 6 . 213 . V o l w i l e r , ¥ . , G r i n d l a y , J . H . & B o l l m a n , J . L . The R e l a t i o n o f P o r t a l V e i n Pressure t o the Format ion o f A s c i t e s - an expe r imen ta l s t u d y . Gas t roen te ro logy - l i t : 1+0, 1950. 211+. Wakim, K . G . & Mann, F . C . The I n t r a h e p a t i c C i r c u l a t i o n o f B l o o d . A n a t . Rec . - 82 : 233, February 191+2. 2 1 5 . Wakim, K . G . E f f e c t s o f A d r e n a l i n and Nembutal Anaes thes ia on B l o o d C o n s t i t u a n t s Before and A f t e r Splenectomy. J . L a b . & C l i n . Med. - 3 1 : 18 , 191+6. 2 1 6 . Wang, C . I . & W a l c o t t , W.W. E f f e c t s o f Anaes thes i a on B l e e d i n g Volume i n the Dog. Am. J . P h y s i o l . - 170: li+3, 1952. 217 . Wermuth, E . G . Anastomoses Between R e c t a l and U t e r i n e Ve ins Forming a Connexion Between the Somatic and P o r t a l Venous System i n the R e c t o - u t e r i n e Pouch. J . A n a t . - 7U$ 116, 1 9 3 9 - U 0 . 218 . Wiggers , C . J . Presen t S ta tus o f the Shock Problem. P h y s i o l o g i c a l Reviews - 2 2 : 7l+, 191+2. 219 . Wiggers , C . J . , Opdyke, D . F . & Johnson, J . R . P o r t a l Pressure Grad ien ts Under Expe r imen ta l C o n d i t i o n s , I n c l u d i n g Haemorrhagic Shock. Am. J . P h y s i o l . - ll+6: 192, 191+6. 2 2 0 . W i l e s , C . E . , Schenk, W.G. & L indenberg , J . Inf luence o f Hepat ic A r t e r y L i g a t i o n on Regenera t ion o f L i v e r Tissue i n the R a t . A . M . A . A r c h . S u r g . - 6 U : 7 8 3 , 1952. 221 . W i n t e r n i t z , M . C . The E f f e c t o f O c c l u s i o n o f the V a r i o u s Hepa t ic V e s s e l s Upon the L i v e r . B u l l . Johns Hopkins Hosp. - 2 2 : 3 9 6 , 1911. 2 2 2 . Wolbach, S . B . & S a i k i , T . A New Anaerobic Sporebearing Bac te r ium Commonly Present i n L i v e r o f H e a l t h Dogs. J . Med. Res . - 21: 267, 1 9 0 9 . 2 2 3 . Wu, P . P . T . The Maximal Volume o f the Human S p l e e n . S u r g . , G y n . , Obst . - 77 : 71+, 191+3. 22l+. Z a n e t t i , M . E . S i g n i f i c a n c e o f E l e v a t e d P o r t a l V e i n P ressure i n E t i o l o g y o f Haemorrhagic Shock. Am. J . P h y s i o l . - 171: 5 3 8 , 1953. 2 2 5 . Zimmerman, H . M . I n f a r c t s o f the L i v e r and the Mechanism o f The i r P r o d u c t i o n . A r c h . P a t h . - 1 0 : 6 6 , 1930. 2 2 6 . Zwei fach , B . W . , Hershey, S . G . , Rovens t ine , E . A . , Lee , R . E . & Chambers, R . Anaes the t i c Agent a F a c t o r i n C i r c u l a t i n g R e a c t i o n Induced b y Haemorrhage. S u r g . - 1$: 1+8, 191+5.

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