Pathology of Cardiac Xenograft Rejection

  • A. G. Rose


Rejection of cardiac xenografts between closely related species may be exclusively acute (cellular) (e.g. Cynomolgus monkey to baboon) or it may be due to a mixture of vascular (hyperacute or delayed vascular/humoral-mediated) and acute rejection (e.g. vervet monkey to baboon). Rejection of xenografts between distantly related species (e.g. pig to baboon) is always by a hyperacute mechanism in the untreated model. Though the acute response can be delayed, or even prevented, by currently available immunosuppressive agents and techniques, hyperacute rejection (Figures 1-7) has proved extremely difficult to prevent or delay. Cardiac xenografts have very occasionally been used in humans in a desperate attempt to save the life of a patient for whom no human donor heart was available[1]’[3] (Chapter 82). Xenogeneic (and allogeneic in sensitized hosts) cardiac transplants, which have been performed in a wide range of experimental animals, have helped to further our understanding of the mechanism of hyperacute rejection[4]’[36] (Chapter 80).


Acute Rejection Cardiac Allograft Acute Cellular Rejection Hyperacute Rejection Cardiac Allograft Rejection 


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  1. 1.
    Hardy JD, Chavez CM, Kurrus FE et al. Heart transplantation in man: development studies and report of a case. J Am Med Assoc. 1964;188:1132.Google Scholar
  2. 2.
    Barnard CN, Wolpowitz A, Losman JG. Heterotopic cardiac transplantation with a xenograft for assistance of the left heart in cardiogenic shock after cardiopulmonary bypass. S Afr Med J. 1977;52:1035.PubMedGoogle Scholar
  3. 3.
    Bailey LL, Nehlsen-Cannarella SL, Conception W. Jolley WB. Baboon-to-human cardiac xenotransplantation in a neonate. J Am Med Assoc. 1985;254:3321.CrossRefGoogle Scholar
  4. 4.
    Kissmeyer-Nielsen F, Olsen S, Peterson VP, Fjeldborg O. Hyperacute rejection of kidney allografts associated with preexisting humoral antibodies against donor cells. Lancet, 1966;2:662.PubMedCrossRefGoogle Scholar
  5. 5.
    Mullerworth MM, Lixlield W, Rachkewich RA et al. Hyperacute rejection of heterotopic heart allografts in dogs. Transplantation. 1972;13:570.PubMedCrossRefGoogle Scholar
  6. 6.
    Rose AG, Cooper DKC. Venular thrombosis: a key event in the pathogenesis of hyperacute rejection (Submitted).Google Scholar
  7. 7.
    Forbes RDC, Guttman RD, Kuramochi T, Klassen J, Knack J. Non-essential role of neutrophils as mediators of hyperacute cardiac allograft rejection in the rat. Lab Invest. 1976:34:229.PubMedGoogle Scholar
  8. 8.
    Forbes RD, Guttmann RD, Bazin H. Hyperacute rejection of cardiac allogralts in a rat strain with a hereditary platelet function defect. Lab Invest. 1977;37:1418.Google Scholar
  9. 9.
    O’Rcgan CC, Robitaille P, Pinto-Blonde M, Chartrand C. Delayed rejection of cardiac xenografts in C6-deficient rabbits. Immunology. 1979;38:245.Google Scholar
  10. 10.
    Forbes RD, Pinto-Blonde M, Guttmann RD. The effect of anticomplementary cobra venom factor on hyperacute rat cardiac allograft rejection. Lab Invest. 1978;39:463.PubMedGoogle Scholar
  11. 11.
    Kobayashi T, Taniguchi S, Ye Y et al. Delayed xenograft rejection in C3-depleled discordant (pig-to-baboon) cardiac xenografts treated with cobra venom factor. Transplant Proc. (In press).Google Scholar
  12. 12.
    Rose AG, Kobayashi T, Kosanke S, White DJG, Cooper DKC. Histopathology of delayed vascular (humoral) rejection in C3-depleted discordant (pig-to-baboon) cardiac xenografts treated with cobra venom factor (CVF)-prominent role of venular thrombosis. (Submitted).Google Scholar
  13. 13.
    Cooper DKC, Human PA, Lexer G et al. Effects of cyclosporin and antibody adsorption on pig cardiac xenograft survival in the baboon. J Heart Transplant. 1988;7:238.PubMedGoogle Scholar
  14. 14.
    Rose AG, Cooper DKC, Human PA, Reichenspurner H, Reichart B. Histopathology of hyperacute rejection of the heart-experimental and clinical observations in allografts and xenografts. J Heart Lung Transplant. 1991;10:223.PubMedGoogle Scholar
  15. 15.
    Sharma HM, Rosensweig J, Chatterjee S, Moore S, De Champlain ML. Platelets in hyperacute rejection of heterotopic cardiac allografts in presensitized dogs. Am J Pathol. 1973;70:155.Google Scholar
  16. 16.
    Rose AG, Cooper DKC. An histopathologic grading system of hyperacute (humoral, antibody-mediated) cardiac xenograft and allograft rejection. J Heart Lung Transplant. (In press).Google Scholar
  17. 17.
    Cattell V, Jamieson SW. Hyperacute rejection of guinea-pig to rat cardiac xenografts. I. Morphology. J. Pathol. 1975;115:183.PubMedCrossRefGoogle Scholar
  18. 18.
    Cony RJ, Kelley SE. Survival of cardiac xenografts. Effect of anlilhymocyte serum and enhancing heteroantiserum. Arch Surg. 1975;110:1143.Google Scholar
  19. 19.
    Jamieson SW. Modification of the hyperacute rejection reaction in the rat by sulphinpyrazone. Thromb Diath Haemorrh. 1975;30:349.Google Scholar
  20. 20.
    Levenlhal JR, Dalmasso AP, Cromwell JW et al. Prolongation of cardiac xenograft survival by depletion of complement. Transplantation. 1993;55:857.CrossRefGoogle Scholar
  21. 21.
    Pcrper R, Najarian J. Experimental renal heterotransplantation. I. In widely divergent species. Transplantation. 1966;4:377.CrossRefGoogle Scholar
  22. 22.
    Michler RE, McManus RP, Smith CR et al. Prolongation of primate cardiac xenograft survival with cyclosporin. Transplantation. 1987;44:632.PubMedCrossRefGoogle Scholar
  23. 23.
    Caves PK, Dong E, Morris RE. Hyperacute rejection of orthotopic cardiac allografts in dogs following solubilized antigen pre-treatment. Transplantation. 1973;16:252.PubMedCrossRefGoogle Scholar
  24. 24.
    Gutlmann RD. Genetics of acute rejection of rat cardiac allografts and a model of hyperacute rejection. Transplantation. 1974;17:383.CrossRefGoogle Scholar
  25. 25.
    Jamieson SW. Xenograft hyperacute rejection. Transplantalion. 1974;17:533.CrossRefGoogle Scholar
  26. 26.
    Kuwahara O, Kondo Y, Kuramochi T et al. Organ specificity in hvperacute rejection of canine heart and kidney allografts. Ann Surg. 1974;180:72.PubMedCrossRefGoogle Scholar
  27. 27.
    Whittum JA, Lindquist RR. Mechanism of cardiac allograft rejection in the inbred rat: the effect of complement depletion by cobra venom factor on hyperacute cardiac allograft rejection. Transplantation. 1977;24:226.PubMedCrossRefGoogle Scholar
  28. 28.
    Guttmann RD. In vitro correlates of rejection. I. Suppressive effect and specificity in mixed lymphocyte interaction of alloanliserum producing hyperacute rejection. Transplant Proc. 1977;9:755.PubMedGoogle Scholar
  29. 29.
    Forbes RD, Guttmann RD, Kuramochi T. Controlled studies of the pathogenesis of hyperacute cardiac allograft rejection in actively immunized recipients. Transplant Proc. 1977;9:301.PubMedGoogle Scholar
  30. 30.
    Guttmann RD. In vitro correlates of rejection. II. Rat mixed lymphocyte reactivity in vitro and cardiac allograft acute rejection, hyperacute or accelerated rejection, and prolongation by active immunization. Transplantation. 1977;23:153.PubMedCrossRefGoogle Scholar
  31. 31.
    Forbes RD, Guttmann RD, Pinto-Blonde M. A passive transfer model of hyperacute rat cardiac allograft rejection. Lab Invest. 1979;41:348.PubMedGoogle Scholar
  32. 32.
    Guttmann D, Bazin H. Lack of significance of allograft differences in hyperacute rejection of rat cardiac allografts. Transplantation. 1979;28:155.PubMedCrossRefGoogle Scholar
  33. 33.
    Coleman DA, Kichwald EJ. Hyperacute rejection of allografted murine hearts and the white graft reaction. Transplantation. 1978;26:355.PubMedCrossRefGoogle Scholar
  34. 34.
    Lexer G, Cooper DKC, Rose AG et al. Hvperacute rejection in a discordant (pig to baboon) cardiac xenograft model. J Heart Transplant. 1986;5:411.PubMedGoogle Scholar
  35. 35.
    Cooper DKC, Lexer G, Rose AG et al. Cardiac allograft survival in ABO blood group incompatible baboons. Transplant Proc. 1987;19:1036.PubMedGoogle Scholar
  36. 36.
    Lexer G, Cooper DKC, Wicomb WN et al. Cardiac transplantation using discordant xenografts in a non-human primate model. Transplant Proc. 1987;19:1153.PubMedGoogle Scholar
  37. 37.
    Cooper DKC, Human PA, Reichart B. Prolongation of cardiac xenograft (vervet monkey to baboon) function by a combination of total lymphoid irradiation and immunosuppressive drug therapy. Transplant Proc. 1987; 19:4441.PubMedGoogle Scholar
  38. 38.
    Cooper DKC, Human PA, Rose AG. Is ABO compatibility essential in xenografting between closely related species? Transplant Proc. 1987; 19:4437.PubMedGoogle Scholar
  39. 39.
    Trento A, Hardesty RL, Griffith BP et al. Role of the antibody to vascular endothelial cells in hyperacute rejection in patients undergoing cardiac transplantation. J Thorac Cardiovasc Surg. 1988;95:37.PubMedGoogle Scholar
  40. 40.
    Cooper DKC, Lexer G, Rose AG et al. Cardiac allotransplantation across major blood group barriers in the baboon. J Med Primalol. 1988;17:333.Google Scholar
  41. 41.
    Reichenspurner H, Human PA, Bochm DM et al. Optimalization of immunosuppression after xenogeneic heart transplantation in primates. J Heart Transplant. 1989;8:200.PubMedGoogle Scholar
  42. 42.
    Cooper DKC, Human PA, Rose AG et al. The role of ABO blood group compatibility in heart transplantation between closely related animal species. J Thorac Cardiovasc Surg. 1989;97:447.PubMedGoogle Scholar
  43. 43.
    Reemtsma K, Pierson RN, Marboe CC et al. Will atherosclerosis limit clinical xenografting? Transplant Proc. 1987;19:108.PubMedGoogle Scholar

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© Kluwer Academic Publishers 1996

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  • A. G. Rose

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