SURGERY Gynecology & Obstetrics

Edrtor, LOYAL DAVIS Associatr Edrtors WALTER CV. CARROLL . F. JOHN LEWIS hfICHAEL L. MASON JAMES T. PRIESTLEY Consulting Edrtors UNITED STATES AND CANADA BRIAN BLADES . JOHN C. BLIRCtI FREDERICK 12'. COOPER, JR . OSCAK CREECII, JR. \YILLIAh4 P. LONGMIRE, JR. . IAN hlACDONALD ANGUS D. hfcLACHLIN . S. IV. h1OORE HAROLD A. SOFIELD . JAMES C WHITE

GREAT BRITAW IAN AIRD . HEDLEY ATKINS JOHN BRUCE. W. ARTHUR hl.4CKEY SIR JAMES PATERSON ROSS ARGENTINA CARLOS A. TANTURI AUSTRALIA KENNETH W. STARR DENMARK E. DAHL-IVERSEN FRANCE REN~FONTAINE ITALY PIETRO VALDON1 NORWAY CARL SEMB SWEDEN PHILIP SANDBLOM uauauAY PEDRO LARGHERO YBARZ

VOLUME 111 JULY TO DECEMBER 1960

Published by THE FRANKLIN H. MARTIN MEMORIAL FOUNDATION 54 EAST ERIE STREET, CHICAGO 11, ILLINOIS, USA. RECON!5TRUCTIVE PROBLEMS IN CANINE LIVER HOMOTRANSPLANTATION WITH SPECIAL REFERENCE TO THE POSTOPERATIVE ROLE OF HEPATIC VENOUS FLOW

T. E. STARZL, hi.D., Ph.D., HARRY A. KAUPP, JR., hl.D., DONALD R. BROCli, hl.D., ROBERT E. LAZARUS, B.A., and ROBERT V. JOHNSON, M.D., Chicago, lllinois

a ALTHOUGHconsiderable experimental data weights of the donor and recipient animals have accumulated concerning many organs, were closely matched. Both dogs were anes- there have been few reports of homotrans- thetized with 25 to 30 milligrams of sodium plantation of the liver. Until 1959, the only pentobarbital per kilogram and, after tra- work had been done by Welch and his as- cheal intubation, placed on respirators. sociates (9, 34), who were able to obtain The arterial pressure of the recipient dog function from liver homografts transplanted was monitored during and immediately into the pelvis. Recently, Moore and his after operation with an arterial catheter associates presented the first accounts of connected to an aneroid manometer. Ve- successful homotransplantation of the ca- nous pressures were read directly from a nine liver to animals with total hepatectomy water manometer attached to an indwelling (21,22). Maximum survival after operation catheter. The operation was performed was 12 days. under sterile conditions by two, or occa- The techniques to be described for homo- sionally three surgeons. In analysis of re- transplantation of the liver have previously sults, the first 27 hepatic transplants were been briefly outlined (1 2, 28). The influence excluded from consideration because a of portal flow upon the homografted liver variety of methods of liver preparation were has been analyzed in detail not only be- used with a resultant inconstant quality of cause this factor proved to be an important grafts. determinant of success or failure but also be- cause the resultant information may have PRELIMINARY STEPS IN THE RECIPIENT DOG application in a variety of other experi- The abdomen was opened with an upper mental situations, including those involving midline incision. A segment of aorta, 1% to hemorrhagic shock. Maximum survival af- 2 centimeters in length, was mobilized just ter liver homotransplantation has been 20% above the inferior mesenteric artery for days. later anastomosis. Next, the mesentery oi the caudate lobe of the liver was incised, and GENERAL METHODS the inferior vena cava encircled with a tape, 1 Seventy-nine liver transplants were per- above the entrance of the adrenal veins. The formed, king healthy adult mongrel dogs gastrohepatic ligament to the left of the por- of 10 to 25 kilograms. In most cases, the tal triad was then doubly ligated and divid- I From the Departments of Surgery and Pathology, North- ed. Finally, common duct and gastroduo- western Uniwrity Medical School, Chicago. denal artery were doubly ligated and di- Aided by Grant A-3176 from the U. S. Public Health Service, National htitutu of Health. Betheada, Maryland. vided as close to the duodenum as possible. 734 Surgery, Gynecology w Obstetrics . December 1960

FIG. 1. Basic technique of homotransplantation. a, Ilonor liver readv for transplant. Note aortic graft removed in continuity with hepatic artery and livcr graft. b, Rccipicnt with portacaval shunt and liver removed. c, Donor liver in place.

'The portal vein was cleaned off toward the mosis was co~npleted,the abdominal wound liver until its bifurcation was encountered, was closed with towel clips, and attentioil taking care to ligate all lymphatics on its sur- directed to the donor dog. face. When these steps were completed, the only uninterrupted structures remaining in PREPARATION OF THE DONOR LIVER the gastrohepatic ligament were the hepatic During this operation on the recipient, artery and the portal vein. the donor dog was immersed in an ice bath. .A portacaval shunt was then constructed and the body temperature reduced to 25 to in as inferior a position as was convenient 30 degrees C. The abdomen of the donor dog (Fig. lb). The exact size and technique of was opened through a long midline incision. this shunt varied with the different tech- The abdominal aorta was mobilized proxi- niques of venous reconstruction during im- mally to the level of the superior mesenteric plantation, but in every case the presence of artery, ligating and dividing all branches the anastomosis was necessary for decom- (Fig. 2). The superior mesenteric artery was pression of the splanchnic system during im- encircled with a ligature but left intact for plantation of the liver. \Vhen the anasto- the time being. Star21 cf al.: RECONSTRUCrIVE PROBLEMS IN CANINE LIVER HOhlOTRANSPWNTATIOK. 735 Next, the stomach and spleen were re- tracted sharply to the right, and the celiac axis was dissected free from its origin to the trifurcation, where splenic and left gastric arteries were ligated and divided (Fig. 2). Attention was then directed to the portal triad. The gastrohepatic ligament to the left of the triad was first ligated and di- vided, and the common duct and gastro- duodenal artery doubly ligated and di- vided near the duodenum. The portal vein was freed from its surrounding adventitia in which there were many lymph channels which required ligation. In order to obtain an adequate length of portal vein for sub- sequent anastomosis, the pancreatic vein was doubly ligated and divided. Several large lymph nodes usually still loosely con- nected the portal vein and hepatic artery inferiorly, but these were stripped out easily with blunt dissection, leaving the hepatic artery and portal vein skeletonized (Fig. 2). Bottle 1 The donor liver was now ready for perfusion f blood ) in situ. FIG.2. Preparation of donor livc-r. :\ortic graft pre- The previously placed ligature around pared. Perfusion of cooled Rinaer's solurion by gravity through the portal vein and collection of blood from the the superior mesenteric artery was tied. The aorta. portal vein was ligated as far inferiorly as possible, and the blunt end of a standard rhage after the liver is revascularized. A intravenous infusion set directed up the por- small incision in the gallbladder was made tal vein to the liver. Through this, 1,000 at the site of the proposed cholecystenteros- cubic centimeters of cooled (5 to 10 degrees tomy to prevent autolysis. The liver was C.) lactated Ringer's solution were used for then brought to the table of the recipient gravity perfusion of the liver with a pressure animal. head of 60 to 80 centimeters of water (Fig. 2). Before evolving this method for prep- As soon as perfusion was begun, the animal aration of the donor liver, a number of un- was bled to death through a catheter inserted satisfactory techniques were employed. into the aorta (Fig. 2). The collected blood These failed generally either because of the was subsequently used for transfusion of the use of heparin in the donor with consequent recipient. During the perfusion, the interior bleeding after transplantation or because of the liver cooled to 10 to 20 degrees C. the liver was not cooled enough to with- The liver was then removed after incision stand the effects of ischemia. of the diaphragmatic ligaments by tran- section of the portal vein, the upper ab- HEPATECTOMY IN THE RECIPIENT DOC AND dominal aorta, and the vena cava above and TRANSPLANTATION OF THE DONOR LIVER below the liver (Fig. la). The open upper After removal of the donor liver, the oper- end of the aortic graft was ligated. The vena ating team returned immediately to the re- caval cuff above the liver was carefully cipient dog and inserted an external poly- scrutinized for small holes which, if unrecog- ethylene bypass from the femoral to jugular nized, will lead to air embolus or hemor- veins (Fig. 3), as described by Kaupp and 736 Surge~,G~rzecology w Obstetrics . Decembe Re-establishment of the portal and vena caval return was done in three different ways (Fig. 5). The choice of procedure in- fluenced the type of portacaval shunt pre- viously performed (during preliminary steps in the recipient dog). The first method of venous reconstruction employed the prin- ciple of the reverse Eck fistula (Fig. 5a), in which the preliminary portacaval shunt was made at least 1 centimeter in length. After completion of the caval-caval anas- tomosis above the liver, an end-to-end por- tal-portal anastomosis was performed, and the open stumps of donor and recipient vena cava below the liver were ligated (Fig. 5a). With release of the clamps, the venous re- turn of both the caval and splanchnic sys- tems were directed through the liver (Fig. 5a). The second method resulted in anatomic venous reconstruction with the addition of a small portacaval shunt (Fig. 5b). In this case, the preliminary portacaval anasto- mosis was made small, 4 to 7 millimeters long, without the excision of an ellipse from Fro. 3. Decornprrss~onof portal and caval venous sys- either vessel. After completing the upper tems during complete occlusion of vena cava and portal vein by external shunt from fcmoral vein to external jug- caval-caval anastomosis, the lower caval-to- ular vein. caval and portal-to-portal anastomoses were performed in anatomic position (Figs. lc Starzl (13). ;\fter liqation and division of and 5b). the hepatic artery, the vena cava, above and The third method of venous reconstruc- below the liver, and the portal vein were tion resulted in normal venous pathways. grasped with Potts' clamps and the liver was The preliminary portacaval anastomosis removed (Fig. 3). .A brisk flow through the was 8 to 10 millimeters in length and was external shunt caused decompression of the used only to decompress the portal system blocked splanchnlc as well as of the caval (via the external polyethylene bypass) beds. during the period of acute portal-caval oc- The cooled donor liver was positioned in clusion as the liver was implanted. The por- the upper part of the abdomen of the re- tal-portal and lower caval-caval anasto- cipient animal (Fig. 1a and b). r\nastomosis moses were performed anatomically with was performed with continuous No. 5-0 ar- No. 6-0 and No. 5-0 silk respectively (Fig. terial silk between the cuff of recipient vena lc). Before the abdomen was closed the cava at the diaphraqm, which was sharply portacaval shunt was taken down and tile pulled down to facilitate exposure (Fig. 4), venotomies were closed with NO. 6-0 ar- and the short cuff of vena cava on the donor terial silk (Fig. 5c). liver. Because of the limited space and short After completing the venous anastomoses, segments of vessels, it was necessary to sew the aortic graft was placed in the right para- the posterior row from within the vessels vertebral gutter and attached with an end- (Fig. 4). to-side anastomosis to the recipient dog's Starzl ct 41.: RECONSTRU~~IVEPROBLEMS IN CANINE LIVER HO~~OTRANSPLANTATIOX 737 aorta, at a variable distance below the renal arteries (Fig. lc). No. 6-0 arterial silk was used and a button of recipient aorta re- moved. Internal biliary drainage was performed with a cholecystojejunostomy, below which was established a jejunojejunostomy (Fig. 40~~s Ant YOW lc). Both gastrointestinal anastomoses were Post. ro\\- performed with a two-layer catgut and silk FIG.4. Technique of caval-caval anastomosis with pos- technique. Splenectomy was carried out, terior row being sutured from within. and the abdomen was closed with multiple layers of fine silk. hemorrhagic gastroenteritis, as a result of hemorrhage from small capsular tears in the POSTOPERATIVE CARE distended liver, or from acute hepatic failure. One million units of aqueous penicillin In preparation of the donor liver, it was were given on the morning of operation and important that the liver be cool before any twice daily during the entire postoperative ischemia occurred. For this reason, total period. As soon as the operation was com- body cooling (25 to 30 degrees C.) was pleted, a large gastric tube was passed and carried out in the donor dog before the ab- kept in position until no longer tolerated. domen was opened. In tlle eLventof acciden- Frequent endotracheal aspirations or bron- tal ischemia during dissection of the portal choscopies were performed until the animal triad or aortic pedicle. before the liver was was fully awake. further cooled by perfusion, some protectio~l During operation, 500 cubic centimeters was afforded. of blood were generally given. During the After the liver had been perfused with first 8 to 10 postoperative hours, it was al- cold Ringer's solution, its temperature was most always necessary to give another 500 well maintained at approximately 10 to 16 cubic centimeters, even to those dogs in degrees C. after removal. Shown in Figure which no bleeding could ever be demon- 6 is a typical warming curve of the interior strated. Intravenous fluids were usually ad- of a donor liver, in which the temperature ministered for the first 2 or 3 days, after rise was less than 2 degrees C. in 1% hours. which many dogs tolerated a low protein Th value of the external bypass during liver diet. If the animals stopped eating, intra- transplantation. In performing the first 20 venous or clysis therapy was reinstituted. liver transplants, an external bypass was not used during the period of portacaval RESULTS Tolerance of the devascularized liver to ischemia. The time between removal of the cooled do- nor liver and its revascularization in the re- cipient dog was 45 minutes, at the least, and in many instances 2 hours. After more than 2 hours, ischemic liver injury occurred which almost always precluded success by any of the described means of reconstruc- tion. When blood flow was restored after ischemia of longer than 2 hours, the liver became tense and dark in color, with his- FIG. 5. Methods of venous reconstruction. a, Reverse Eck fistula. b, Anatomic reconstruction with small porta- tologic evidence of intense congestion. caval shunt. c, Complete anatomic reconstruction with Death followed in a few hours either from closure of preliminary portacaval shunt. 738 Surgery, (;vnecology Q Obstetrics . Decembe to 4 days, in 11 experiments as a result 20 1 of the inability of the transplanted liver to transmit the required venous flow, with consequent hemorrhagic gastroenteritis. The other early deaths were caused by hemor- rhage in 3 dogs, portal thrombosis in 3 dogs, atelectasis in 2 dogs, air embolus in 1 dog, and unknown etiology in 2 dogs. Most of the unsuccessful experiments fol- lowed a highly characteristic pattern. After revascularization, it became obvious that sequestration of blood was occurring in the liver which became swollen, tense, and ex- tremely dark in color. Shortly after. large amounts of lymphatic fluid escaped from FIG. 6. Rewarm~nqcurve of interior of donor liver exposed to room temperature lor I pi hours. the surface of the liver capsule. The portal vein and inferior vena cava distended with occlusion. since in previous work it had been pressures as high as 250 millimeters of saline. determined that sl~ortterm occlusion in the Superficial lacerations in the transplanted presence of a portacaval shunt was well tol- liver began to hemorrhage, and frequently erated (20). Sur\.ivals of as long as 6 days the previously dry portal-portal or porta- were obtainrd \%.it11 tt~istechnique, but in caval anastomosis began to ooze, sometimes subsequent espcr-iments the external bypass uncontrollably. Within a few minutes, the was routinel>. w,ed for sei~eralreasons. The bowel and stomach lost their normal pink portacaval occlusion was often for as long as color and assumed a faintly cyanotic hue. 2 hours, durinq the latter part of which pro- Within a few hours, large quantities of fluid found hypotcnsion i~sually developed. At accumulated in the gut-at first clear and autopsy. many of the doqs had cardiac le- later blood-stained. sions similar to tl~einfarcts described by In such cases, a progressively increasing Tanturi afrer tt.rnporarv portal occlusion. rate of blood transfusion was necessary to Finally, I~cmorrhaqicqastroenteritis proved maintain the blood pressure. Bloody diar- to be a common postoperative complication, rhea developed, and the animals died in 5 to and it was not possible to know if this was 15 hours, despite aggressive therapy. Histo- due to the acute portal hypertension during logic sections of the liver showed acute con- implantrition or to splanchnic venous stasis gestion and early disruption of hepatic cord which developed postoperatively. architecture (Fig. 7a). Sections of the large With tlle esternal bypass, severe hypo- and small intestine revealed marked con- tension did not develop. Some fall in blood gestion and interstitial edema of the entire pressure occurred. but the mean pressure wall (Fig. 8a and b). almost always remained above 100 milli- In other experiments, the animals sur- meters of mercury. The bowel remained vived the immediate postoperative period, pink. Clottin3 of the siliconized tube did not only to die 1 to 4 days postoperatively, generally occur during the bypass. usually from gastrointestinal hemorrhage. 'lcute egect of venous reconstruction with the In these animals, there was histologic evi- reverse Eckfirtula. 'Twenty-six hepatic trans- dence of persistent hepatic congestion with plants were performed by the method of the distention and coalescence of sinusoids (Fig. reverse Eck fistula (Fig. 5a). Only 4 of the 7b). Hepatic cell loss was apparent, espe- 26 dogs survived for more than 4 days. The cially in central areas. Associated slough of' other 22 animals died at varying times up intestinal mucosa and inflammatory in- I;lc:. -. I Jrstolocic rhanecs in ticpatic outflow block. a. 1.1vc.r aftcr 10 IIOIII-9. sl~o\\lnc c.onarstlon and earl\. loss of arc11itcrtu1.c\\.it11 dilated sinusoids. b. Anothrr li\.c.r at 30 l~ourcS~ICI\\ Inc pcrslstrnt conerstlon and rnarkcd disorcanization of hcpatir architrrtl~l.~.X214. liltration of intestinal \villi occurrecl (Fig. ative period: 3 of I~cn~orrl~aqc.4 of atel- 8c). cctasis. 3 of IicmorrI~aqi(~qnstroenteritis. I Four of tllc 36 liver transplants rcvascu- as a result of por1;11tl~ro~~~l~osis. .\I) impor- Iarized with tllr reverse Eck fistula sur\.ivecl tant contributor). c.;iusc. 01' cleat11 in manv or longer than 4 da!.s. or long enough for 110- tlicse dogs was a tlisrincri\.c syndrome toll- ~liograftrejection to l)c espected to occur. sisting of intractable \.oniitin~and retching Maximum sur\.i\.al was 9 days. whicli began imlnediatcly after operation Numerous complications characterizecl and continued until rllc deatll of tt~edog. this group of animals. Formation of ascites This was thou~l~t.but not pro\.ed. to be due bvas excessi\.c. and dissection of the fluid to acute liver failure. through the incision with ~voundbreakdown With this technicluc. tllc acutc congestion occurred in all long term survivals. Pneu- of the liver and bo\vcl dcscribcd for the re- monitis and thrombosis of the vascular anas- verse Eck fistula \vas seen in onl). 3 experi- tomosis were also late causes of death. Onl). ments. Cienerall)., the li\,rr becanle soft and 1 of the long term survivors was able to eat. light in color after re\.ascularization, and Acute eject of analomic zlenous reconstruction the bowel remained pi~ikexcept in those with addition of a portacarial shunt. Fifteen cases in which the shunt was inadvertently transplants were performed by means of made too small to be functional. anatomic reconstruction of the venous sys- Despite the obvious disadvantage of re- tem with the addition of a small portacaval ducing the blood flow to the liver, this tech- shunt (Fig. 5b) . The portacaval anasto- nique of reconstruction proved to be the mosis was deliberately constructed small- most versatile in one respect. It was possible 4 to 7 millimeters-so that a definitely ele- to perform transplantation without closely vated portal pressure would be necessary in matching the size of 111sdonor and recip- order for large flows to cross the shunt. In ient animals. Donors were used which this way, it was hoped to decompress the weighed as much as 8 to 10 kilograms less liver and splanchnic circulation in the event than the recipient animals. a disparity in of high portal pressures. without unneces- size which precluded success in the other sarily diverting portal blood from the liver. two methods because of the development of Fifteen livers were transplanted in this man- splanchnic and hepatic congestion. ner and 6 animals survived for more than 4 Six of the 15 dogs \vith this type of venous days. Nine dogs died in the early postoper- reconstruction lived for more than 4 days. 740 Surger?, Gjnecology G Obstetrics . December 1'960

FIG. 8. Intestinal changes resulting from outflow hepatic block in dogs with reverse Eck fistula. a, Small intestine after 10 hours showing mucosal and subrnucosal congestion and submucosal ede- ma. Note intact epithelium. X11. b, Small intestine in another dog after 18 houn. There is congestion and loss of epithelium of distal portions of villi. X44. c, Small intestine in a dog dying after 36 hours. Base of villi have partially intact epithelium, but distal villi are edematous and con- gated with marked slough of epithelial covering. X44.

Only 2 animals were able to eat consistently. other methods, as did maximum survival Maximum survival was 9 days. Although it which was 20% days. is thought that homograft rejection oc- curred, a variety of other complications DISCUSSION were found at autopsy which could have The unusual susceptibility of the liver to been independent causes of death. anoxia has undoubtedly deterred proqres.; Acute efect of anatomic renous reconstruction. in hepatic transplantaion. Welch and asso- Eleven dogs Iiad reconstitution of the liver ciates (9), who transplanted the whole (11.- in an anatomic manner, and 8 survived for gan to the pelvis of recipient dogs, pointetl more than 4 days. The causes of early death out that the transferred tissue could not sur- were hemorrhagic gastroenteritis in 2 cases, vive if devascularized for more than 30 and atelectasis in the third. When this tech- minutes under normothermic conditions. nique was used, the acute bowel congestion Disclosures of the protective effect of hypo- described with reverse Eck fistula recon- thermia on the ischemic liver by Raffuci, struction was seldom encountered provided Bernhard, and Huggins and their associates the weights of the donor and recipient dogs have made transplantation studies morr were closely matched. However, efforts to practical. use significantly smaller donor than recip- Despite the protection of hypothermia. ient animals resulted in acute bowel con- undue prolongation of ischemia results in ;I gestion and early death. characteristic liver injury in which the re- The clinical behavior of this group of dogs vascularized organ entraps large quan- was the most satisfactory of all techniques tities of blood. The inability of blood to es- tried. ,411 8 long term dogs resumed oral in- cape is probably due to constriction of small take promptly, usually after 2 days, and con- intraparenchymal hepatic veins as shown tinued to eat until shortly before death, by Deysach and Thomas and Essex. These which was presumably due to liver rejec- vessels have been demonstrated by Arey to tion. The average long term survival ex- have extraordinarily well developed mus- ceeded that obtained with either of the cular coats in the dog. Similar hepatic con- Starzl el al.: RECONSTRUC~NE PROBLE gestion, aptly termed "blue liver syndrome" liver with increased hepatic vein outflow, as or "outflow block." has been described in shown by Bauer and his associates and by the dog in a variety of physiologic circum- Maegaith, while acetylcholine has a less stances including: anaphylaxis and peptone pronounced but reverse effect. From this shock by Mautner and Pick, Simonds, and information, it would seem quite possible Weil; temporary devascularization of the that the denervated liver undergoes vaso- liver by Hines and Roncoroni and State motor alterations which promote stasis. and Lichtenstein; histamine injection by Such a mechanism. in addition to contrib- Mautner and Pick and Bauer and his asso- uting to outflow block, could explain the ne- ciates; perfusion of the isolated liver by cessity for the large transfusions which are Makravarti and Tripod, Maegaith, and necessary postoperatively, even in the dogs Kestens and his associates; endotoxin shock which survive for long term study. by MacLean and Weil; and hemorrhagic The sequence of events in the bowel fol- shock by Frank (6) and Wiggers and their lowing outflow block in the transplanted associates. liver is of interest because of the resemblance With transplantation of the liver, the de- of the pathologic changes to those seen in gree of ischemic injury is only one of the in- irreversible hemorrhagic shock. For many fluences which contribute to the grave com- years, the liver has been suspected of playing plication of outflow block. The most impor- an important role in the development of ir- tan t secondary factor is the volume of venous reversibility. Numerous observers, including blood which is transported to the liver. In Selkurt (25), Wiggers. and Friedman and the normal dog, it has been shown by Meyer their associates, have reported increased and others that both the splanchnic and in- hepatic vascular resistance after experi- ferior caval venous return can be directed mental hemorrhage, and it has been rea- through the liver without harmful effects. sonable to believe that consequent splanch- But the anoxic transplanted liver apparently nic pooling and reduction of circulating reacts to such augmented venous flow with blood volume would result. This concept outfiow block. In contrast, the blue liver de- was apparently strengthened by the demon- veloped infrequently when venous inflow stration of Fine and his associates (7) that was normal or when a decompressing porta- viviperfusion of the liver during hemor- caval anastomosis was retained as a perma- rhage prevented the hemorrhagic gastro- nent feature of the reconstruction. The im- enteritis of irreversible shock. However, portance of regulating portal vein inflow in Fine's group (6) also demonstrated that avoiding outflow block during isolated liver decompression of the portal system with perfusion has also been commented upon by portacaval shunt to prevent impounding of McDermott and, associates (14), as well as blood in the splanchnic system did not pre- numerous earlier workers. vent the intestinal lesions. Subsequently, at- Another factor contributing to the suscep- tention has been focused on other than he- tibility to outflow block of the transplanted patic factors in irreversibility, and recently or the isolated perfused liver may be the the intestine itself has been suggested as an state of denervation in both instances. The important primary target organ in shock by confusing literature on vasomotor control Schweinburg and his associates, Selkurt, of the liver has been summarized by Child. ELillehei. The dominant autonomic influence appears The assessment of the relative importance to be sympathetic, with reduction of the size t e liver and that of bowel in determining of the liver and increased outflow upon irreversibility of shock is still not settled, al- stimulation. Parasympathetic stimulation though there is evidence that both play an has resulted in less clear findings. Similarly, important role. In the present study, an ex- epinephrine solutions cause shrinkage of the perimental situation was present in which 742 Surgery, G~n~cologyG Obstetrics . December BERNHARD,W. F., MCMURREY,J. D., and CURTIS, only the liver was subjected to anoxia. The G. W. Feasibility of partial hepatic resection under blood pressure generally was never below hypothermia. N. England J. M., 1955, 253: 159. CHILD,C. G. The Hepatic Circulation and Portal 100 before, duriny, or immediately after Hypertension. Pp. 90-106. Philadelphia: W. B. liver was revascularized. Yet, in the dogs de- Saunders Co., 1954. DEYSACH,L. J. The nature and location of the veloping outflow hepatic block, shock soon "sphincter mechanism" in the liver as determined ensued which ultimately was intractable to by drug actions .and vascular injections. Am. J. further transfusion and which eventuated in Physiol., 1941, 132: 713. FRANK,H. A., GLOTZEN,P., JACOB, S. W., and FINE, fatal hemorrhagic gastroenteritis. In this J. Traumatic shock -XIX, hemorrhagic shock in Eck fistula dogs. Am. J. Physiol., 1951, 167: 508. situation, the damage inflicted upon the FRANK,H. A., SELIGMAN,A. M., and FINE,J. Trau- liver by the transplantation would seem to matic shock -XIII, the prevention of irreversi- bility in hemorrhagic shock by viviperfusion of the be solely responsible for the inception and liver. J. Clin. Invest., 1946, 25: 22, development of irreversible shock. FRIEDMAN,E. W., FRANK,H. A., and FINE,J. Portal circulation in experimental hemorrhagic shock; in SUMMARY vivo roentgen ray studies. Ann. Surg., 1951,134: 70. GOODRICH,E. O., WELCH,H. F., NELSON,J. A,, The homologous canine liver has been BEECHER,T. S., and WELCH,C. S. Homotransplan- tation of the canine liver. Surgery, 1956, 39: 244. transplanted to recipient animals in which HINES,J. R., and RONCORONI,M. Acute hepatic total hepatectomv and splenectomy have ischemia in dogs. Surg. Gyn. Obst., 1956, 102: 689. HUGGINS,C., CARTER,E., and MCDERMOTT,W. been performed. The longest survival after Differential hypothermia in experimental hepatic placement of the liver homograft was 20% surgery. Arch. Surg., 1957, 74: 327. KAUPP,H. A., LAZARUS,R. E., and STARZL,T. E. days. Complete homotransplantation of the liver after to- Protection from hepatic ischemia for as tal hepatectomy in dogs. (Abstract) Presented at the American Association for Study of Liver Disease. long as 3 hours \vas obtained by coolin5 the Chicago, Nov. 5, 1959. Gastroenterology, 1960, 38: donor liver to 10 to 20 degrees C. The ar- 794. KAUPP,H. A., and STARZL,T. E. The use of an ex- terial suppl). \\.;ls restored through a hepatic ternal by-pass durinq experimental total hepatec- artery-aortic pedicle which was removed in tomy. Surgery, in press. KESTENS,P. J., AUSTEN,W. G., and MCDERMOTT, continui tv \vi th t lle liver and anastomosed W. V., JR. Biochemical and physiologic studies on to the descendin? aorta of the recipient. In- the viable extracorporeal liver. Surgical Forum: Clinical Conqress 1059. \'ol. X, p. 225. Chicago: ternal biliary drainage was established. American Colle~eof Surqeons, 1960. The \.olurnc of \.cnous flow transmitted to IJLLEHEI,K. C. The intestinal factor in irreversible hrmorrhaqic shock. Surqerv, 1957, 42: 1043. the transplanted li\.er has been shown to be MACLEAN,L. D.. and Ct'cr~, M. H. Hypotension an important dett.rminant of success. When (shock) in doqs produced bv I.;scherichia coli endo- toxin. Circ. Kes., 1956, 4: 546. this was cscessivc. as when both the portal ~~AECAITII,B. G. hlicroanatomy of the hepatic vas- and infcrior caval fowsweredirected throuqh cular system. Trans. Tenth Conf., May 21-22, 1951. Josiah Macy Jr. Foundation, 1951, pp. 181-204. the liver, hcpatic outflow block usually de- ~IAKRAVARTI,M., and TRIPOD,J. 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