Daloze, PM

Huguet, C

Porter, KA

Starzl, TE

English

PubMed

D-Scholarship@Pitt

AIL7XILIARJr LIOJIOTR,ISSPL,\ST,ITIOS OF TIIE C~ISIST.; LII7ER \VITII TIIE I'SE OF ,I ''REVERSE" JYELCII TECHSI(J['E P I E R R E  J L  I).iI,OZE. 11.1). ('LA\[-DE HTGUET. 11.1). TiES A\. PORTER, -\I.I)., I).Sc. 'I'HOJZAS E. STAHZL. Ph.l)., J1.U. 1)enver. ('010. From the Department of Surgery Un~versity oP Colorado School of Jle<lrc~ne And Veterans dtlnlln~strat~on Hosp~tal  Reprinted from SYRGERT St. LOlllh Vol. 04. S o .  5, Paqes !l.14-9:$!). Sovenll,er, l9fjH (Couyriaht 0 1968 by TheC V. JIosby Company) (Printed In the U. S. A,)  Ausilinrv homotransplantation of the canine liver with the use PIERRE M. DALOZE, M.D." of a "reverse" 1lTelch technique D uring recent years. i t  has been estab- lished that auxiliary liver ho~nografts \\-hi& are placed in ectopic locations can undergo involution by other means than rejection. The prototype of this operation was described by Welch13 and Goodrich and associates.= They placed the extra liver in the riyht para- vertebral gutter. The hepatic arterial supply \\.as derived from the aorta or iliac artery. Venous inflow was reconstituted by anasto- xnosing the distal iliac vein or inferior vena cava to the homograft portal vein. It  has been shown that the total blood flo~v to such \Selch homografts is equal to that in the d o ~ ' s  own undisturbed liver.? Nevertheless, e\.en though the transplanted or, eans are protected from rejection by host immuno- suppression, they atrophy1" in a way not seen in orthotopic homografts that are nor- mally vascularized in the liver fossa. Previous studies from our laboratory:. have provided a simple physiological ex- planation for the atrophy, and one \\.hich has been confirmed and extended by other  investigator^.^^ 9 9  l1 When txvo livers or sepa- rate liver fragments coexist. they appear to compete for metabolites. The nutritional sub- strate or substrates are apparently highly extractable by the liver and are present in This work w a  supported by United States Public Health Service Grants AM-06344. HE-07735. .4\1-117772. AI- 04152, FR-00051, FR-00069. AM-12148, and .\I-08898. Received for publication Fcb. 9, 1968. *Fellow of the McLaushlin Foundation, Toronto. CLAUDE HUGCET, M.D. KEN -4. PORTER. M.D., D.Sc. THOMAS E. STAIIZL, PH.D.. M.D. DENVER. COLO. From the Department of Surgery, Cniversity o f  Colorado School of Medicine and Veterans Administration Hospital the highest concentrations in nonhepatic splanchnic blood. Thus: if all other condi- tions includiny the volume of blood flow are equal. a piece of liver which is perfused by the intestinal venous effluent has an advan- tage over a companion hepatic fragment lvhich has had its portal flow replaced from systemic venous sources; the latter unfavored liver tissue undergoes rapid atrophy and de- glyco~enation.; Factors other than the quan- tity and quality of the blood supply can in- fluence the outcome of such an experiment. For example, the competitive ability can be reduced by obstructing the biliary drainage1' and presumably anything else which causes liver injury would have this disabling effect. In experiments with auxiliary homotrans- plantation, there is by definition an inherent inequality of the two organs since the homo- graft is under immunologic attack and the animal's own liver is not. This was well illustrated by Halqrirnson and co-workers,; \vho demonstrated that, if only an arterial supply were provided to each of the two organs, the homograft invariably underwent selective atrophy. As shown by Marchioro and co- worker^.^ Halgrimson and co-workers," and others," l1 the graft atrophy could be re- duced by giving the auxiliary liver a dis- proportionately great blood supply, especially if this included a portal inflow from the non- hepatic splanchnic bed.8 In the present study, a new modification of auxiliary transplantation was designed in order to further test the interrelationship 934 SURGERY November, 1968 VoI. 64, No. 5 ,  pp. 934-999 ry, LTniversity of nd Feterans is in nonhepatic i all other condi- of blood flow are ich is perfused by ,nt has an advan- !iepatic f r a p e ~ t  iow replaced from .e latter unfavored .I atrophy and de- .er than the quan- lod supply can in- ch an experiment. [ive ability can be biliary drainaye" else which causes .is disabling effect. siliary homotrans- nition an inherent ns since the homo- ic attack and the ~ t .  This was \veil and co-workers.' E only an arterial each of the t ~ v o  ariablv undenvent Lvn by Marchioro ,n and co-workers.' :rophy could be re- iiliarv liver a dis- t i  supply, especially Flow from the non- I new modification in was designed ixi e interrelationship Volume 64 Number 5 "Reverse" Welch technique for liver i~omotransplantation 935 between host and graft livers in immuno- suppressed dogs. The results indicate that vven diversion of all splanchnic venous flow throuyh the hon~ograft cannot prevent its atrophy if the recipient liver receives a cIuantitatively similar blood flow from non- splanchnic sources. These tindinys may be important in assessing the feasibility of ausili- ary transplantation for the treatment of dis- vases such as congenital hiliarv atrcsia i11 \vtlich a considerable functional reserve mav still be present in the diseased host liver. METHODS O f  the 24 experiments performed. only the 1 1  brought to completion lvill be considered further. The auxiliary transplantations were between unrelated mongrel dogs. T h e  recipi- ents weighed 13.2 to 19 kilograms and the donors were selected for an  approximate size match. Homografts were weighed a t  the time of operation and inserted as shown in Fig. 1. The  important features of the opera- tion included the facts that  the blood leaving the homograft did not pass through the portal system of the recipient's own liver. that instead the host portal inflow was de- rived entirely from systemic venous blood which in turn bypassed the auxiliary liver. and that the splanchnic return from the host intestines all passed through the homograft. Durinq the time when the suprarenal inferior vena cava was transected, the animals were heparinized and the venous pool decom- Fig. 1. Technique used for transplanting auxiliary livers. Note that the host liver is revascular- ized in the same way as with portacaval transposition. The ectopically homograft re- ceives nonhepatic splanchnic blood. The features of the blood supply to the respective organs are thus the opposite of those in the classical Welch preparation. 4 .  No. 5, fib 934-939 936 Dalore et al. pressed with an  external plastic femorojugu- 1ar bypass. Postoperative immunosuppression was with heteroloqous antilyrnphocyte glob- 1tli11 (ALG) , azathioprine. and prednisone .IS pl cviousiy described.l -4ntibiotics were :l\-C'Il. 'Flit. an i~~ la l s  \\.ere follo~ved tvith frequent I~c~natologic and biweekly li\.er iunction stud- icss. .-liter one 2nd three lveeks. they lvere nncsthctizcd \\.it11 pentobarbital and phen- c!.clidine liydrochloride and re-examined surgically. Biopsy specimens Ivere obtained irom the livers. \-enograms were obtained ~v i th  catheters inserted into the iemoral vein and lnese~lteric \.enous branches. and venous Inessures \\ere nieasured lvith the use of the c5timated le\.cl of the rirri~t atrium as a I~aseline. 111 four doqs, catheters were then t)l.ouglit csternally a t  the time of the three- \vrt.L study for blood flow measurement a clay later ill the awake state ~v i th  the tccllniclue as described elsewhere2* the Icrnoral and mesenteric catheters were used to i~lject into the aritoloeous liver and the homocrnit respectively. The  same procedures \;-?re repeated at  six weeks in dons that lived tliis loriq. Surqery November  1968 LYheri the animal died or was put to death. the pntcncy of anastomoses was veri- fied. Final tissues \\.ere taken for pathologic (:?taminntion. Both the host liver and the homoqraft were dissected free of extraticorls tissue and weiyhed. RESULTS In  eiglit recipients, all the vascular anas- tomoses remained patent. Hereafter. these doas are classified as belonging to Group I. T h e  other three animals developed thrombo- sis at  the cavoportal anastomosis throuqh which the portal flow to the autologous liver rvas dependent. The host organ thus even- tually had only an arterial supply: the latter dogs constituted Group 11. The  doqs of hoth zroups lost \veiqht 10.5 to 5.5 kiloqrams~ and had early marked and later chronic low-grade elevations in serum ~ l u t a m i c  oxaloacetic transaminase (SGOT) , serum glutamic pyruvic transaminase ( SGPT), and alkaline phosphatase. They did not become jaundiced or develop ascites. ,Anemia was common. There \vere no overt differences in the clinical beha~.ior of members of Groups I and 11. Table I. . l~~ . \ i / i n r ,~~  lirrr tra?rs!~lantatio?z 1 Blood flow at .7 mk. 1 1  1 Homograft  weight (ml./mzn./IOO C I I I .  Sur:,i:,ai I / G m . )  Hoct iirer rceicht I :isrue i .Yo. I /rlavsi lReiectionir1t operation; . j t  death I E.ctimatedx 1 .it death Homonrnit i Host ii:,er Group I .  All nnustotnores patent 1 56 f  S l i l d  ", 9 208 2 16 294 226 199 1 22 Sone  7 6 7  295 160 250 - 3 5 SIod. :i 36 263 3 95 413 198 204 4 4 Severe 11 2 204 371  494 303 245 5 39f Sc\.erc 5 1 2  !34t 3 95 399 - - 6 38 \l i l t1 313 230 367 360 247 276 7 20 Xiild :345 .I-J 3 28 365 - - r, ,> - 8 23 Sone  104 - - - - 310 328 330 - - -   Mean 35.6 :324: 262: 340: 358: 2 +4 1 3  1 Group 11. Cacoportal anastomores clotted 1 17 Severe 230 130 371 389 - - 2 1 2  Sone  274 9 10 330 320 - - 3 74: Severe 344 - - - - 220 328 310 - - - \lean 31.3 2 8 ;  220 . ? j O  2 .w - - -.Estimated as 2.8 percent oi hodv u ~ i z h r .  :These animals \\ere put to death. The ottwrs died of pneumonitis ( 3 ) .  extrapulmonary sepsis ( 3 ) ,  o r  intussusrcption ( 2 ) .  :Dog 5 excluded from averape because of divided spianchnic drainase. Surgery November 1968 )r was put to :noses was veri- for pathologic liver and the :I oi estrancorls \ asc~11ar nnas- !creak ter. these !iy to Group I. ioped thrornbo- ~mosis throurrh  toloy lo yo us liver :an thus cven- r~plv. the latter ' tc docs ol both i 5 hllo, "I a ~ n s  I later t lironic I um qlr~tamic GOT' .  serum e I SGPT). and . ~ d  not become -. .inernla was r r t  differences I members of Volume 64 Surnber  5 "Rcrvrre" TVelch technique for liver homotransplantation 937 Surgery ~Vouember 1968 Group I. I n  7 of the 8 dogs, the anyio- ,C-ranls sholced passage of r.rna caval flo\e into the recipicnt liver (Fiq. 2. :1 i, and ap- ~~aren t ly  complete drainage of the splanchnic i~cci through the homoqraft (Fig. 2. B ) .  The crntral pressures in the respective venous ~vstcrns \\.(,re 8.8 : 3.6 (S.D.) and 13.8 i- 2.0 : S.D.! cln. H,O. Do? 5 had a tributary ~ . l~tcr iny thc portal vein above the site oi  licarion. I n  this case. the dye injected in the nonhepatic splanchnic system appeared ill both livers (Fig. 2, C i .  There were four c~speri~nents in which technically satisfactory blood flow measurements were obtained at  3 ~ceeks. The values were approximately the same for the homograft and host livers iTable I ) .  The honloqraft ~eeiyhts a t  operation and at  clrath from 20 to 56 days later are given in Table I. There was a significant weight loss in 4 of the T auxiliary livers ~ehich re- (-eived ~lndivided splanchnic flow. I n  con- trast. there rcas no evidence of atrophy in the autoloyous organs; the anticipated \rt.i:hts of the host livers. computed as 2.8 per cent of the total body \\-eiqht,' conformed \\ell to those actually measured after death 1 71-~ble I \ . knee the pathologic f indin~s in the homo- cratts and host li\ers were ~encrallv similar to those previously reported after auxiliary transplantation.:, these will not be described ayain. However, the findinqs from study of the biopsy specimens and postmortem tissues of the homoyrafts were reviewed and an over-all evaluation ~ i v e n  of the deqree of carlv plus late rejection (the grading is sum- marized in Table I , . Group II. Comparable data on survival, lixer ~teiqhts, and patholo~ic yradinys are summarized in Table I. The finding are subject to the resewation that the times \\hen cavoportal occlusion occurred were not known. DISCUSSION The procedure used for these experiments mirrht be considered a "reverse" Welch operation. In  Welch's preparation, the au- toloyous 1iLc.r liad a normal blood supply \chi]? t lic liornoyaft was vascularized in the u lne  way as with a portacaval trans- position. 111 contrast. the host liver in our .~nimals leas subjected to the transposition and portal flow was directed throuyh the llomoqrait. LVith this change, extreme homoqraft atrophy xvas avoided. 111 three of the seven animals in which all the splanchnic flow seemed by angiography to pass to the homo- graft. there was little or no weiyht loss of the transplant; in the other four the cleqrce of atrophy was moderate, compared to that seen in LVelch-type auxiliarv livers.'' The improvement was evidently not due to an imbalance in the volume of blood flow to the dual orqans. I t  has been shown that the blood flow to the two livers after LVelch's procedure is equivalent'; the same finding pertained in the present study. Instead. the partial protection of the homografts was probably the result of perfusing it with splanchnic venous blood accordinq to the concept developed by Marchioro and asso- ciates.' and confirmed by Price and asso- ciates.!' The incompleteness of the homo- qraft protection in contrast to that previously described by Marchioro and associatess Leas explicable by the fact that there was a more normal total volume of flow to the host liver than in Marchioro's original experi- ments. The  fact that  some homograft atrophv commonly occurred despite its perfusion with splanchnic venous blood adds a further pre- cautionary note about the wisdom of auxili- arv hepatic transplantation to patients \chose own livers possess significant residual func- tion. I n  a competitive environment. primary exposure to splanchnic blood flow is a physio- logic advantage but one which may not be sufficient if the homoyraft is subjected to the injury of severe but potentially reversible rejection. Under the latter circumstance, the only hope for long-term transplant function may be if the new orxan is unopposed. as is the case with orthotopic homotransplanta- tion. Surgery Nouember 1968 iionnal blood supply was vascularized i l l  11 a portacaval trans- the host liver in our 1 to the transposition directed throuqh thc extreme homoql at t In three of the se\rn the splanchnlc flat% 5 to pass to the homo- or no weicht loss ot other four the decree ate. compared to that tuxiliary licers.1° The  Jentlv not due to an Ime of blood flow to > been shown that the ) livers after \Yelch 5 ~ t - :  the same findlnq nt studv. Instead. the the homografts \\as )t perfusing it \\ ,ti1 sod according to the Marchioro and asso- i bv Price and asso- teness of the homo- rast to that previouslv o and associates* \ \ a \  :hat there lvas a molt= of flow to the host oro's original espcri- z homograft atrophy ,spite its perfusion \vith ~d adds a further pre- the wisdom of ausiii- :tion to patients \\..hose iificant residual func- environment. prima? blood flow is a physio- ie which may not be craft is subjected to : potentially reversible tter circumstance. the .n transplant function ..in is unopposed. as is pic homotransplanta- Volume  6.1 "Reverse" Welch technique for liver homotransplantation 939 Number  5 SUMMARY .A~~.uiliary liver homogralts were revascu- larized in the lower abdomen of dogs with an  arterial blood supply from the aorta and Ivith a portal venous supply that was derived from the host splanchnic bed. Tlie animals' o\vn livers were deprived of splanchnic flow but this was replaced ivith s!.sternic venous I~lood. Total hepatic blood flow in the CO- clsisting livers \vas approximately equal. Un- der these conditions the homograft atrophy often seen after auxiliary transplantation was reduced but not prevented. The findings have been discussed as thev relate to the rnechanisrn of homoqraft atrophy and to the applicabilitv of such techniques for the treat- ment of human disease. REFERENCES 1. Brettschneider, L., Daloze. P. M., Huguet. C., Porter, K. A., Groth. C. G., Kashiwagi, N., Hutchison, D. E., and Stanl. T .  E.: The use of combined preservation techniques for ex- tended storage of orthotopic liver homoerafts, Surg. Gynec. & Obst. 126: 263. 1968. 2. Daloze. P. M., Huguet. C.. Groth. C .  G., and Stoll, F : Blood flow in auxiliary canine liver homoerafts. In  press. 3. Goodrich. E. O., Welch. H. F.. Selson. J. A., Beecher, T .  A., and \Velch. C. S.: Homo- transplantation of the canine liver, SURGERY 39: 2-14. 1956. 4. Groth, C. G., Porter. K. .4., Otte. J. B., Daloze, P. M., Marchioro, T. L.. Brett- schneider. L,, and Starzl. T .  E.: Studies of blood flow and ultrastructural changes in rejecting and nonrejecting canine orthotopic liver homografts. SURGERY 63: 658, 1968. 5. Halgrimson, C. G., Marchioro, T. L., Faris, T. D., Porter. K. A,, Peters. G. N., and Starzl, T .  E.: .4uxiliary liver transplantation: Effect of host portacaval shunt, -4rch. Surg. 93: 107, 1966. 6. Lee. S.. and Edginton, T .  S.: Liver trans- plantation in the rat, S. Forum 17: 220, 1966. 7 .  Marchioro. T. L., Porter, K. .4., Brown, B. I., Otte, J. B., and Starzl, T. E.: The effect of partial portacaval transposition on the canine liver, SURGERY 61: 723, 1967. 8. Marchioro. T. L., Porter, K. -4.. Dickinson, T. C., Faris. T. D.. and Starzl, T .  E.: Physio- logic requirements for auxiliary liver homo- transplantation, Surg. Gynec. & Obst. 121: 17, 1965. 9. Price. J. B., Voorhees, A. B., Jr . ,  and Brit- ton, R. C.: The role of portal blood in re- generation and function of completely revas- cularized hepatic autografts, SURGERY 62: 195, 1967. 10. Starzl, T .  E., Marchioro, T. L., Rowlands, D. T.. Kirkpatrick. C. H., Wilson, W. E. C., Rifkind, D., and Waddell, W. R.: Immuno- suppression after experimental and clinical homotransplantation of the liver, Ann. Surg. 160: 41 1. 1964. 11. Tretbar, L. L.. Beven, E. G., and Hermann, R. E.: The effects of portacaval shunt and portal flow occlusion on canine auxiliary liver homotransplants, SURGERY 61: 733, 1967. 12. Van der Heyde. N. H., Schalm, L.. and Vink. M.: The role of functional competition in  auxiliary liver transplantation, Transplan- tation 5: 78. 1967. 13. Welch, C. S.: A note on the transplantation of the whole liver in dogs, Transplant. Bull. 2: 54, 1955. 

Auxiliary homotransplantation of the canine liver with the use of a "reverse" Welch technique.

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Auxiliary homotransplantation of the canine liver with the use of a "reverse" Welch technique

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Auxiliary homotransplantation of the canine liver with the use of a "reverse" Welch technique.

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