Barrett, B

Kukral, JC

Neyman, B

Riveron, E

Starzl, TE

Vaitys, S

Weaver, J

PubMed

Name not available

Metabolism of plasma protein fractions after orthotopic homografts and autografts of the dog liver

D-Scholarship@Pitt

METABOLISM OF PLASMA PROTEIN FRACTIONS AFTER ORTHOTOPIC HOMOGRAFTS AND AUTOGRAFTS OF T H E  DOG LIVER JOHN C. KUKRAL, M.D., EMILIO RIVERON, M.D., JOHN WEAVER, M.D., BEN NEYMAN, PH.D., STEPHANIE VAITYS, B.S., BARBARA BARRETT, B.S., AND THOMAS E. STARZL, M.D., F.A.C.S. PLASMA PROTEIN ABNORMALITIES are observed following transplanta- tation of various tissues (1-5). The  exact nature and significance of these changes remains unclear. The  present study was designed to distinguish between protein changes related to the surgical stress of transplantation and those which are related to the unmodified homo- graft rejection mechanism. METHODS Plasma protein concentrations, synthesis, and turnover indices were determined for 7 plasma protein fractions before and after hepatic transplantation in 14 dogs. All dogs received 250 PC. S35 methionine intravenously; and blood samples were drawn at intervals of 3,6,9,12, 24, and 7 2  hr., and thereafter at 5, 7, 10, 14, 21, and 35 days. Repeat studies were done on all dogs on the fourth day after: a) orthotbpic homografts of liver from unlabeled animals, recipient Group 1-4 dogs; b) orthotopic homografts of liver from labeled animals, Group 11-5 dogs; c) orthotopic autografts, control Group 111-5 dogs. All anastomoses were anatomical except for biliarv continuity which was via a cholecystojejunostomy in Groups I and 11. In all groups the liver was cooled prior to transplantation with iced Ringer's lac- tate by portal vein perfusion for 10 to 15 min. No immunosuppres- sive drugs were used. All blood samples were separated into serum and plasma and analyzed for concentration (milligrams per cent) and specific radioactivity (counts/min./mg. protein). Paper block elec- trophoreses were used to separate the albumin and globulin fractions and fibrinogen and seromucoid were determined by thrombin precipi- tation, and by phosphotungstic acid precipitation respectively. RESULTS A 20y0 to llOyo rise in the concentration of all plasma protein fractions was noted after all transplantations except the albumin From the Surgical and Radioisotope Services, University of Illinois College of Medicine, Northwestern University Medical School, and West Side and Research Veteran Administration Hospitals, Chicago. Supported by U. S .  Public Health Service Grant Am-10444. Reprint from Vol. XVII, Surgical Foruna, .4lnerican College o f  Surgeons, 1966 fraction which showed a 20% to 80% decrease. Greatest increases were noted in the glycoprotein rich fractions of a globulins, fibrino- gen, and seromucoid. Increases in circulating levels were correlated with 50% to 200% increases of S3j uptake (synthesis) and increased S3j disappearance with shorter half-lives (turnover). The  albumin fraction showed a 40% to 80y0 increase in uptake (synthesis). Only the y globulin fraction of serum showed a significantly greater increase in concentration, synthesis, and turnover rate after liver homografts than after autografts. The  9 dogs in Groups I and I1 had a mean sur- vival of 12 days. This unusually long survival in untreated animals was largely the result of 2 unique dogs which lived 18 and 31 days. The  animals in Group I11 were killed after 1 year. DISCUSSION Previous studies have shown a lowered albumin concentration and an increased globulin concentration after experimental renal and hepatic transplantation (3, 4). The  reason for lowered albumin re- mains obscure but increases in globulins especially the a globulins were related to a nonspecific inflamatory response (4). The  present study supports this view since changes in albumin and a and p globulins with homografts parallel those seen after autotransplanta- tion. The  additional finding of increased uptake of S35 methionine into albumin (synthesis) in the face of a decreased concentration prob- ably indicates an actual increase in synthesis and turnover in a se- questered albumin pool. The  increase in y globulin concentration and uptake appeared most prominently in the homotransplanted group and most likely represents increased antibody production and turn- over. However. whether vG or .,M is r~rimarilv involved cannot be stated from our data. I t  is known that yM antibodies appear earlier than yG, although this sequence can be altered by immunosuppres- sive drugs (6). CONCLUSION Increases in metabolic turnover of all plasma proteins after liver transplant are due to a nonspecific response to the surgical trauma of transplantation except for the increased synthesis and turnover of the globulins (circulating antibody) which is specifically related to the homograft rejection mechanism. Increases in synthesis and turn- over of albumin with a decrease in concentration suggest increased utilization in a sequestered extravascular space. REFERENCES 1. STARZL, T. E., KAUPP, H. A., BROCK, D. R., LAZARUS, R. E., and JOHNSON, R. V. Reconstructive problems in canine liver homotransplantation. Surg. Gyn. Obst., 1960, 111:733. , 2. KUKRAL, J. C., LITTLEJOHN, M. H., WII.LIAMS, R. D., PANCNER, .  J., BUTZ, G. FV., and STARZL, T. E. Hepatic f~unction after canine liver transplantation. Arch. Surg., 1962, 85:157. 3. MOORE, F. D., WHEELER, H. B., DEMISSIANOS, H. V., SMITH, L. S., BALANKURA, O., ABEL, K., GREENBERC, J .  B., and D ~ M M I N ,  G. J. Experimental whole-organ trans- plantation of the liver and of the spleen. Ann. Surg., 1960, 152374. 4. WEST, C. 1). and NATHAN, P. The  relationship of serum globulins to trans- plant rejection in the dog studied by paper and immuno-electrophoretic tech- niques. Ann. New York Acad. Sci., 1960, 87:522. 5. HUME, D .  hi., MAGEE, J. H., KAUFFMAN, H. hl . ,  JR., RIITENBURY, M. S., and PROUT, G. R., JR. Renal homotransplantation in man in modified recipients. Ann. Surg., 1963, 158:608. 6. SAHIAR, K. and SCHWARTZ, R. S. The  i~nn~unoglobulin sequence. J. Immun., 1965,95:345-354. 

Metabolism of plasma protein fractions after orthotopic homografts and autografts of the dog liver.

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Metabolism of plasma protein fractions after orthotopic homografts and autografts of the dog liver.

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