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.