Denmark, SW

Griffith, BP

Shaw, BW

Starzl, TE

PubMed

Shaw Jr, BW

Name not available

Veno-venous bypass without systemic anticoagulation in canine and human liver transplantation

D-Scholarship@Pitt

VENO-VENOUS BYPASS WITHOUT SYSTEMIC ANTICOAGULATION IN CANINE AND HUMAN LIVER TRANSPLANT ATION Scot W. Denmark, MD, Byers W. Shaw, Jr., MD, Thomas E. Starzl, MD, FACS, and Bartley P. Griffith, MD I/, tC II PREVIOUS A TfEMPTS TO PERFORM liver transplantation during ve~ \ venous bypass with systemic anticoagulation (heparin) in 12 patients a1 I this medical center resulted in excessive blood loss in six and at least one l' fatality. The purpose of this study was to test the plausibility and conse· quences of using a veno-venous circuit without systemic anticoagulatioD during liver transplantation. of MATERIALS AND METHODS Orthotopic liver transplantation was perfonned in ten mongrel dogs (20 to ~R kg) while using the bypass circuit without systemic heparin. Results of hematologic proflles, hemodynamic measurements, and postmortem examination wercK~paredK with those in three dogs in which-80" ln!fi!1-flfffK:"D:·":D:·"=·-~w=as= useo.lbese th1"ee controltransplailtS employed the "cuff' "technique ~ K~F~K described by Coopennan et al (1). Bypass was initiated with drainage ,:: _ from the divided portal vein and proximally occluded infrahepatic vena ~ r... cava with return to an external jugular vein. The circuit consisted of a > '''.'1 . j4 centrifugal. pump an~ trow probe wi~ P/U-~ncb Tygon tubing .coated with D: it; j 5% albumtn and pnmed With a phYSiolOgiC electrolyte solution. Appro-f K~: priately sized Bahnson caval cannulas were used for the jugular vein ~ ;;::: ~ cava, while a fenestrated stainless-steel ventricular vent with 1/4-inch St-::"} lastie tubing drained the portal vein. Bypass continued for two to four k hours at rates of flow between 400 and 1,500 mUmin. In the clinical trial. ~ : caval drainage was obtained through 7-mm Gott tubing introduced via the &L ! right common femoral vein advanced to the iliac vein; the same size was I used for the portal vein, and a 9-mm piece provided venous return to the I patient's left axillary vein. The remainder of the circuit was unchanged. I I RESULTS The use of bypass avoided low cardiac output and portal venous conges-tion usually associated with caval and portal vein occlusion. Hematologic profiles were not significantly different between groups and indicated a slight decrease in RBCs (5.67 to 5.16 x 1()6/mm3), WBCs (13.8 to 9.8 x 10l/mm3), platelets (145 to 117.5 x 10l/mm3), and fibrinogen (145 to 80 mg%/dL) associated with the bypass. Fibrin split products and mon-380 1 TllANSPLANT A nON e moderately elevated (staph c\' omers wer the Sll' 4 +) Fibrin threads were seen on . to . d. . n which the flow rate decre In twO stu les 1 .. f the lun' and microscopic exammau~n 0 . thrombus. In the clinical tnal. PT, ~ '\ slightly during bypass. whereas fibnn p~t and fibrinogen levels decreased. The p pneumonia during the first posto~ratteI tion. no intravascular thrombus was ou, the lung. DISCUSSII The use of a bypass circuit in l.iver advantages by avoiding severe c.anltova hypotension, often associated ~lth cava At completion of the infrahepau~ ven~ ca rich in potassium and hydrogen l~ns IS n _ from the pn:Kviou~!v stagnant ~apl~fary ~ . nie circulationS. A bypass cii'Cl11f that the cava below the liver coul~ prevent t acid which might cause cardiac anh~ different shunts (without a pump) dun.n Partial cardiopulmonary . bypass proV1C human liver transplantatlons perf~lDffiCE . terrucall" investigators used hepann sys f bypass without systemic anticoagulau( during liver transplantation withou~ im thromboembolism and served to sumu cannulas were heparin bonded. 1be us associated with normal cardiac outpUt. nificant change in coagulation factors. and monomers. or thromboelasto~ feasibility of vena-venous bypass Wlt experimental and early clinical sucCt clinical use in human liver tranSplant< REFER! 1. CoopemwI AM. Woods IE. Mclln!h I hepatic ttansplaDtation. Am J SurJ 122:797-8 2. Azpcitia D. De Miguel ~K Jufte A •• :,; stage of transplantation of \be liver (aulbor lITHOUT SYSTEMIC -\NINE AND HUMAN LIVER Byers W. Shaw, Jr .• MD, Thomas md Bartley P. Griffith. MD R!'ORM li~er transplantation during Veno. ,tlcoagulatIOn (heparin) in 12 patients ;cessive blood loss in six and at least 0 II jy. w~ to test the plausibility and con::' ClTCUlt Without systemic anticoagulation • TRANSPLANT AnON 381 onleTS were moderately elevated (staph clumping I to 128. ethanol ge.1 I 10 4 + ). Fibrin threads were seen on the suppon struts of the pum~ hOUSIng in twO studies in which the flow rate decreased below 800 mUmm. Gross and microscopic examination of the lungs failed to show intravascular mrombus. In the clinical trial. PT, Prr, and fibrin monomers increased slightly during bypass, whereas fibrin spl.it products remained unc~an~ed and fibrinogen levels decreased. The patient developed a fatal aspiratIOn pneumonia during the first postoperative week. At postmonem examina-tion, no intravascular thrombus was found at the cannulation siles or in the lung. DISCUSSION I The use of a bypass circuit in liver transplantation provides several ~ AND METHODS t Idvantages by avoiding severe cardiovascular derangements, particularly .n ~asK per:ormed in ten mongrel dogs (20 I hypotension, often associated with caval clamping prior to hepatectomy. . ClqCa~t Without systemic heparin. Results At completion of the infrahepatic vena caval and portal anastomoses, blood jynanuc. measurement~I and postmonem rich in potassium and hydrogen ions is returned to the systemic circulation .h those 10 three dogs 10 which no bypass • from the previously stagnant capillary beds of the lower body and splanch-1lIlspiants employ~ ~e "cuff' technique nic circulations. A bypass circuit that decompresses the portal vein and (I). BrPass was mltlat~ with drainage me cava below the liver could prevent the accumulation of potassium and 1~ promnally occluded mfiahepatic vena acid which might cause cardiac anbythmias. Azpeilia et al used several ~ :". C". -~ t:::r" ........ ;: C~ t::! .• ::::K~ -J ~-~~ --~ r:::.. ~4 --. 1 gu~lar v~inK The circuit consisted of a different shunts: (without a pump) during liver transplantation in dogs (2). ~ ~ ~/~!af~ ~bing coated WIQ' t=:*={,artial cardiopulmonary bypass provided hemodynamic stability during ~K: 1 pbysiologic electrolYte ~jution: Appro.· - uman liver~splantCtilns performed by CaIne et aI El}K::Agl-Kd::It~he~se~-II;:""O ___ .... nnulas were used for the Jugular vein and investigators used heparin systemically. In this experiment, veftO.:'veoous"- ,.. =:. !ss-steel ventricular vent with 1/4-inch Si- bypass without systemic anticoagulation preserved the physiologic state :r~ ; vein. Bypass continued for two to four during liver transplantation without imposing significant coagulopatl)y or ~~ .00 and 1,500 mUmin. In the clinical trial. lhromboembolism and served to stimulate a clinical trial in which bypass t--'ough 7-rnm Gott tubing introduced via the cannulas were heparin bonded. The use of this system in one patient was 5: lanced to the iliac vein; the same size was associated with normal cardiac output. portal decompression, and no sig-9-mm piece provided venous return to the nificant change in coagulation factors, platelet count, fibrin split products : remainder of the circuit was unchanged. and monomers, or thromboelastogram. This study has demonstrated the RESULTS w cardiac output and portal venous conges. v~ and portal vein occlusion. Hematologic different between groups and indicated a 105.16 x 1000/mmJ ), WBCs (13.8 to 9.8 117.5 x 1()3/mmJ). and fibrinogen (145 to .he bypass. Fibrin split products and mon-1""-D~ 5</000/ of Mrtb<int. lDinsbttrI~ 380 feasibility of veno-venous bypass without systemic anticoagulation. The experimental and early clinical success has prompted plans for routine clinical use in human liver transplantation. REFERENCES I. Coopennan AM. Woods IE. McIlrath DC: Simplified method of canine onhotopic hepatic transplantation. Am J Surg 122:797-801. 1971 2. Azpeilia D. De Miguel E. Juffe A. el al: [8ypau lechniques during the anhepalic stage of transplantation of the liver (author's transl»). Ann ChiT 29(2):155-160. 1975 -- KI~--K---~------382 Sl'RGICAL FORt,. 3. Caine RY. Smith DP. McMaster P. et al: Use of partial cardl0pulmonary bype. during the anhepatic phase of orthotopic liver grafting. Lancet 2(81431:612-614. 1979 CYCLOSPORINE TREATMENT FOR LUNG ALLOGRAFT REJECTION IN MONGREL DOGS: INDUCTION OF UNRESPONSIVENESS AND MIXED LYMPHOCYTE AND CYTOLYTIC T-CELL ACTIVITY • , TVJ"lSpLANT AnON RESU The cytolytic activity of recip~ent 1 Jonor lymphocytes was determmed. 'ned from the recipient pnor to tra1 ~ donor lymphocytes for seven da in a four-hour concanavalin A-depenl Jent on the concentration of effector c( to target cell ratio (0) o~ loo:~K T cells after in vivo stimulatIon with a cells from SAL of the lung allograft a1 16 to 21 days after left lung transplar in the lectin-dependent assay. Cytot~ at an Elf of 100: I, and the cytotOXlt 0.7% at an Eff of loo:\. Allen J. Norin, PhD, Eugene E. Emeson, MD, Stephan L. I DISCm V . h MD FACS We have prevIous y Kamholz, MD, Kenneth L. Pinsker, MD, and Frank J. ~ . I shown that spe elt, , '", of the recipie!}(s ~plleralK ?g~ T:: ___ A._ MAJOR GOAL of transplantation risearchTs tlle induction of a ~ta-;- -D:ra~n~~:~~~y:e~~~t~~~pl;~~ of specific unresponsiveness to allografted organs so that immunosup- ( aftertransplantation.ln this report,w , ' , , , pressive therapy could be terminated without subsequent rejection. We I taneous cytolytic activity of T -cells pre. viously reported that single lung allografts in unmatched mongrel d~gs allograft was signifi.cantlY lower tha survived for more than 95 to 420 days after termination of-Cyclosponne cells in MLC that were performed 1 (Cys) therapy (l,2). In this report we compared the cytolytic activity of allograft recipients. we have shown. the prospective recipient's T-cells after mixed lymphocyte culture (MLC) BAL remains relatively constant dun with irradiated donor lymphocytes to the cytolytic activity of the recipi- \ riod, even when Cys therapy is ter:"' ent's T -cells after transplantation. of the initial effects of Cys therapy lS , of cytolytic T -cells in canin~ lung al MATERIALS AND METHODS Left lung allotransplantation was performed in male mongrel dogs (Biomedical Associated Inc, Friedensberg, Penn) as previously described (3). Cys (Sandoz Ltd, Basel, Switzerland) was administered at an initial dose of 17 mglkglday and tapered as detailed elsewhere (2,4). Lung al-lografts were evaluated by chest roentgenogT"clITls, radionucIide ventilation-perfusion lung scans, analysis of cells in BAL and open lung biopsies or necropsies (2,3). Cytolytic T-cell activity was measured in a lectin-de-pendent 5lCr-Iabeled Raji target cell assay as published previously (5,6). The percentage of cytotoxicity was calculated by the formula (cpm 51Cr experimental - cpm 51Cr spontaneous + 51Crmaximum - cpm slCr spon-taneous). One-way MLC were initiated as previously reported (7). F,_ ~~K of Micr~ tutd 1"",,"""'0f)', S"".ry, I'DlItDIory tutd M.diciM. MO'flqwn MrdieaJ c.--Albm EilUlftIt ColI.,. of MHicuw. N ... Yon:. s~ .. i~ pan I1y NIH ,NIN HLJ7417 tutd /M Mnfrr~D c~DDDDD· \ T-cell activity is correlated WIth. reduc , and the induction of unresponslvenes REFERl I.. Nonn AJ, Emeson EE, Veith FJ: r~ after cessation of cydosponn A therapy· 2. Norin AJ. Emc:son EE. Kamholz SL. c ~ive agent for canine lung tta/lsplantaDon phenomena. Transplantation 34:372-375. 19~ 3. Veith Fl, Norin AJ. MontefuSCO 0 transplantation. Transplantation 32:474-481, 4, Nonn AJ, Veith Fl, EmesonEE. et mongrel dogs treated with c:yclos~mn A, Tr 5. Emeson EE. Nonn Al. Veith FJ: ~~ and simple method to quantitative CytotOXIC 369 

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Veno-venous bypass without systemic anticoagulation in canine and human liver transplantation

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